@comment{This file has been generated by Pybliographer} @Article{CHL+95, Author = {Casset, F and Hamelryck, T and Loris, R and Brisson, JR and Tellier, C and Dao-Thi, MH and Wyns, L and Poortmans, F and Perez, S and Imberty, A}, Title = {N{MR}, molecular modeling, and crystallographic studies of lentil lectin-sucrose interaction.}, Journal = {J Biol Chem}, Volume = {270}, Pages = {25619-28}, abstract = {The conformational features of sucrose in the combining site of lentil lectin have been characterized through elucidation of a crystalline complex at 1.9-A resolution, transferred nuclear Overhauser effect experiments performed at 600 Mhz, and molecular modeling. In the crystal, the lentil lectin dimer binds one sucrose molecule per monomer. The locations of 229 water molecules have been identified. NMR experiments have provided 11 transferred NOEs. In parallel, the docking study and conformational analysis of sucrose in the combining site of lentil lectin indicate that three different conformations can be accommodated. Of these, the orientation with lowest energy is identical with the one observed in the crystalline complex and provides good agreement with the observed transferred NOEs. These structural investigations indicate that the bound sucrose has a unique conformation for the glycosidic linkage, close to the one observed in crystalline sucrose, whereas the fructofuranose ring remains relatively flexible and does not exhibit any strong interaction with the protein. Major differences in the hydrogen bonding network of sucrose are found. None of the two inter-residue hydrogen bonds in crystalline sucrose are conserved in the complex with the lectin. Instead, a water molecule bridges hydroxyl groups O2-g and O3-f of sucrose.}, authoraddress = {Institut National de la Recherche Agronomique, Nantes, France.}, country = {UNITED STATES}, keywords = {Comparative Study ; Computer Simulation ; Crystallography, X-Ray ; Hydrogen Bonding ; Lectins/*chemistry ; Ligands ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Molecular Conformation ; Sucrose/*chemistry ; Support, Non-U.S. Gov't}, language = {eng}, medline-da = {19951214}, medline-dcom = {19951214}, medline-edat = {1995/10/27}, medline-is = {0021-9258}, medline-jc = {HIV}, medline-jid = {2985121R}, medline-lr = {20001218}, medline-mhda = {1995/10/27}, medline-pmid = {7592736}, medline-pst = {ppublish}, medline-pt = {Journal Article}, medline-rn = {0 (Lectins) ; 0 (Ligands) ; 0 (lentil lectin) ; 57-50-1 (Sucrose)}, medline-sb = {IM}, medline-so = {J Biol Chem 1995 Oct 27;270(43):25619-28.}, medlineref = {96029650}, year = 1995 } @Article{HDP+96, Author = {Hamelryck, TW and Dao-Thi, MH and Poortmans, F and Chrispeels, MJ and Wyns, L and Loris, R}, Title = {The crystallographic structure of phytohemagglutinin-{L}.}, Journal = {J Biol Chem}, Volume = {271}, Pages = {20479-85}, abstract = {The structure of phytohemagglutinin-L (PHA-L), a leucoagglutinating seed lectin from Phaseolus vulgaris, has been solved with molecular replacement using the coordinates of lentil lectin as model, and refined at a resolution of 2.8 A. The final R-factor of the structure is 20.0\%. The quaternary structure of the PHA-L tetramer differs from the structures of the concanavalin A and peanut lectin tetramers, but resembles the structure of the soybean agglutinin tetramer. PHA-L consists of two canonical legume lectin dimers that pack together through the formation of a close contact between two beta-strands. Of the two covalently bound oligosaccharides per monomer, only one GlcNAc residue per monomer is visible in the electron density. In this article we describe the structure of PHA-L, and we discuss the putative position of the high affinity adenine-binding site present in a number of legume lectins. A comparison with transthyretin, a protein that shows a remarkable resemblance to PHA-L, gives further ground to our proposal.}, authoraddress = {Dienst Ultrastructuur, Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel, Paardenstraat 65, B-1640 Sint-Genesius-Rode, Belgium.}, country = {UNITED STATES}, keywords = {Binding Sites ; Concanavalin A/ultrastructure ; Crystallography, X-Ray ; Models, Molecular ; Phytohemagglutinins/*ultrastructure ; Prealbumin ; Protein Conformation ; Support, Non-U.S. Gov't}, language = {eng}, medline-da = {19961011}, medline-dcom = {19961011}, medline-edat = {1996/08/23}, medline-is = {0021-9258}, medline-jc = {HIV}, medline-jid = {2985121R}, medline-lr = {20001218}, medline-mhda = {1996/08/23}, medline-pmid = {8702788}, medline-pst = {ppublish}, medline-pt = {Journal Article}, medline-rn = {0 (Phytohemagglutinins) ; 0 (Prealbumin) ; 0 (phytohemagglutinin L) ; 11028-71-0 (Concanavalin A)}, medline-sb = {IM}, medline-so = {J Biol Chem 1996 Aug 23;271(34):20479-85.}, medlineref = {96355378}, year = 1996 } @Article{HPG+96, Author = {Hamelryck, TW and Poortmans, F and Goossens, A and Angenon, G and {Van Montagu}, M and Wyns, L and Loris, R}, Title = {Crystal structure of arcelin-5, a lectin-like defense protein from {P}haseolus vulgaris.}, Journal = {J Biol Chem}, Volume = {271}, Pages = {32796-802}, abstract = {In the seeds of the legume plants, a class of sugar-binding proteins with high structural and sequential identity is found, generally called the legume lectins. The seeds of the common bean (Phaseolus vulgaris) contain, besides two such lectins, a lectin-like defense protein called arcelin, in which one sugar binding loop is absent. Here we report the crystal structure of arcelin-5 (Arc5), one of the electrophoretic variants of arcelin, solved at a resolution of 2.7 A. The R factor of the refined structure is 20.6\%, and the free R factor is 27.1\%. The main difference between Arc5 and the legume lectins is the absence of the metal binding loop. The bound metals are necessary for the sugar binding capabilities of the legume lectins and stabilize an Ala-Asp cis-peptide bond. Surprisingly, despite the absence of the metal binding site in Arc5, this cis-peptide bond found in all legume lectin structures is still present, although the Asp residue has been replaced by a Tyr residue. Despite the high identity between the different legume lectin sequences, they show a broad range of quaternary structures. The structures of three different dimers and three different tetramers have been solved. Arc5 crystallized as a monomer, bringing the number of known quaternary structures to seven.}, authoraddress = {Laboratorium voor Ultrastructuur, Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel, Paardenstraat 65, B-1640 Sint-Genesius-Rode, Belgium. thamelry@vub.ac.be}, country = {UNITED STATES}, keywords = {Anti-Infective Agents ; Asparagine/chemistry ; Binding Sites ; Crystallography, X-Ray ; Glycoproteins/*ultrastructure ; Legumes/*chemistry ; Metals/metabolism ; Molecular Sequence Data ; Plant Proteins/*ultrastructure ; Polysaccharides/chemistry ; Protein Conformation ; Support, Non-U.S. Gov't}, language = {eng}, medline-da = {19970123}, medline-dcom = {19970123}, medline-edat = {1996/12/20}, medline-is = {0021-9258}, medline-jc = {HIV}, medline-jid = {2985121R}, medline-lr = {20001218}, medline-mhda = {1996/12/20}, medline-pmid = {8955116}, medline-pst = {ppublish}, medline-pt = {Journal Article}, medline-rn = {0 (Anti-Infective Agents) ; 0 (Glycoproteins) ; 0 (Metals) ; 0 (Plant Proteins) ; 0 (Polysaccharides) ; 158709-58-1 (arcelin 5) ; 7006-34-0 (Asparagine)}, medline-sb = {IM}, medline-si = {PDB/1IOA ; PDB/R1IOASF}, medline-so = {J Biol Chem 1996 Dec 20;271(51):32796-802.}, medlineref = {97115814}, year = 1996 } @Article{DHP+96, Author = {Dao-Thi, MH and Hamelryck, TW and Poortmans, F and Voelker, TA and Chrispeels, MJ and Wyns, L}, Title = {Crystallization of glycosylated and nonglycosylated phytohemagglutinin-{L}.}, Journal = {Proteins}, Volume = {24}, Pages = {134-7}, abstract = {In the seeds of legume plants a class of sugar-binding proteins can be found, generally called legume lectins. In this paper we present the crystallization of phytohemagglutinin-L (PHA-L), a glycosylated lectin from the seeds of the common bean (Phaseolus vulgaris). Single PHA-L crystals were grown by vapor diffusion, using PEG as precipitant. The protein crystallizes in the monoclinic space group C2, and diffracts to a resolution of 2.7 angstroms. The unit cell parameters are a=106.3 angstroms, 121.2 angstroms, c=90.8 angstroms, and beta=93.7 degrees. The asymmetric unit probably contains one PHA-L tetramer. Crystals of a recombinant nonglycosylated form of PHA-L, grown under identical conditions, and crystals of the native PHA-L, grown in the presence of isopropanol, did not survive the mounting process.}, authoraddress = {Laboratorium voor Ultrastructuur, Interuniversitair Instituut voor Moleculaire Biotechnologie, Vrije Universiteit, Brussel, Belgium.}, country = {UNITED STATES}, keywords = {Carbohydrate Sequence ; Crystallography, X-Ray/*methods ; Diffusion ; Glycosylation ; Molecular Sequence Data ; Phytohemagglutinins/*chemistry/*metabolism ; Polyethylene Glycols/chemistry ; Recombinant Proteins/*chemistry/metabolism ; Support, Non-U.S. Gov't}, language = {eng}, medline-aid = {10.1002/(SICI)1097-0134(199601)24:1<134::AID-PROT9>3.0.CO;2-K [pii]}, medline-da = {19960627}, medline-dcom = {19960627}, medline-edat = {1996/01/01}, medline-is = {0887-3585}, medline-jc = {PTS}, medline-jid = {8700181}, medline-lr = {20001218}, medline-mhda = {2000/06/20 09:00}, medline-pmid = {8628728}, medline-pst = {ppublish}, medline-pt = {Journal Article}, medline-rn = {0 (Phytohemagglutinins) ; 0 (Polyethylene Glycols) ; 0 (Recombinant Proteins) ; 0 (phytohemagglutinin L4)}, medline-sb = {IM}, medline-so = {Proteins 1996 Jan;24(1):134-7.}, medlineref = {96211784}, year = 1996 } @Article{LHB+98, Author = {Loris, R and Hamelryck, T and Bouckaert, J and Wyns, L}, Title = {Legume lectin structure.}, Journal = {Biochim Biophys Acta}, Volume = {1383}, Pages = {9-36}, abstract = {The legume lectins are a large family of homologous carbohydrate binding proteins that are found mainly in the seeds of most legume plants. Despite their strong similarity on the level of their amino acid sequences and tertiary structures, their carbohydrate specificities and quaternary structures vary widely. In this review we will focus on the structural features of legume lectins and their complexes with carbohydrates. These will be discussed in the light of recent mutagenesis results when appropriate. Monosaccharide specificity seems to be achieved by the use of a conserved core of residues that hydrogen bond to the sugar, and a variable loop that determines the exact shape of the monosaccharide binding site. The higher affinity for particular oligosaccharides and monosaccharides containing a hydrophobic aglycon results mainly from a few distinct subsites next to the monosaccharide binding site. These subsites consist of a small number of variable residues and are found in both the mannose and galactose specificity groups. The quaternary structures of these proteins form the basis of a higher level of specificity, where the spacing between individual epitopes of multivalent carbohydrates becomes important. This results in homogeneous cross-linked lattices even in mixed precipitation systems, and is of relevance for their effects on the biological activities of cells such as mitogenic responses. Quaternary structure is also thought to play an important role in the high affinity interaction between some legume lectins and adenine and a series of adenine-derived plant hormones. The molecular basis of the variation in quaternary structure in this group of proteins is poorly understood.}, authoraddress = {Laboratorium voor Ultrastruktuur, Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel, Sint-Genesius-Rode, Belgium. reloris@vub.ac.be remy@ultr.vub.ac.be}, country = {NETHERLANDS}, keywords = {Carbohydrate Sequence ; Concanavalin A/chemistry ; Dimerization ; Lectins/*chemistry ; Legumes/*chemistry ; Models, Molecular ; Molecular Sequence Data ; Mutagenesis, Site-Directed ; Protein Conformation ; Support, Non-U.S. Gov't}, language = {eng}, medline-da = {19980430}, medline-dcom = {19980430}, medline-edat = {1998/04/18 02:15}, medline-is = {0006-3002}, medline-jc = {A0W}, medline-jid = {0217513}, medline-lr = {20001218}, medline-mhda = {1998/04/18 02:15}, medline-pmid = {9546043}, medline-pst = {ppublish}, medline-pt = {Journal Article ; Review ; Review, Academic}, medline-rf = {157}, medline-rn = {0 (Lectins) ; 11028-71-0 (Concanavalin A)}, medline-sb = {IM}, medline-so = {Biochim Biophys Acta 1998 Mar 3;1383(1):9-36.}, medlineref = {98207687}, year = 1998 } @Article{DHB+98, Author = {Dao-Thi, MH and Hamelryck, TW and Bouckaert, J and Korber, F and Burkow, V and Poortmans, F and Etzler, M and Strecker, G and Wyns, L and Loris, R}, Title = {Crystallization of two related lectins from the legume plant {D}olichos biflorus.}, Journal = {Acta Crystallogr D Biol Crystallogr}, Volume = {54}, Pages = {1446-9}, abstract = {The seed lectin DBL and the related stem and leaves lectin DB58 of the tropical legume Dolichos biflorus were crystallized, as well as complexes of DBL with adenine and with GalNAc(alpha1-3)[Fuc(alpha1-2)]Gal. The different crystal forms of DBL diffract to about 2.8 A, while DB58 crystals diffract to 3.3 A.}, authoraddress = {Laboratorium voor Ultrastructuur, Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel, Paardenstraat 65, B-1640 Sint-Genesius-Rode, Belgium.}, country = {DENMARK}, keywords = {Adenine/metabolism ; Carbohydrate Sequence ; Crystallization ; Crystallography, X-Ray ; Lectins/*chemistry/isolation \& purification/metabolism ; Macromolecular Systems ; Molecular Sequence Data ; Oligosaccharides/metabolism ; Receptors, Mitogen/metabolism ; Recombinant Fusion Proteins/chemistry/isolation \& purification/metabolism ; Support, Non-U.S. Gov't}, language = {eng}, medline-da = {19990601}, medline-dcom = {19990601}, medline-edat = {1999/03/25 03:01}, medline-is = {0907-4449}, medline-jc = {C3C}, medline-jid = {9305878}, medline-lr = {20001218}, medline-mhda = {2000/06/23 11:00}, medline-pmid = {10089534}, medline-pst = {ppublish}, medline-pt = {Journal Article}, medline-rn = {0 (DB58 lectin, Dolichos biflorus) ; 0 (Dolichos biflorus lectin receptor) ; 0 (Lectins) ; 0 (Macromolecular Systems) ; 0 (Oligosaccharides) ; 0 (Receptors, Mitogen) ; 0 (Recombinant Fusion Proteins) ; 0 (blood group A trisaccharide) ; 0 (dolichos biflorus agglutinin) ; 73-24-5 (Adenine)}, medline-sb = {IM}, medline-so = {Acta Crystallogr D Biol Crystallogr 1998 Nov 1;54(2 ( Pt 6)):1446-9.}, medline-url = {http://www.iucr.org/journals/acta/tocs/actad/1998/actad5406.html\#GR0820}, medlineref = {99192704}, year = 1998 } @Article{HLB+99, Author = {Hamelryck, T.W. and Loris, R. and Bouckaert, J. and Wyns, L}, Title = {Properties and {S}tructure of the {L}egume {L}ectin {F}amily.}, Journal = {Trends Glycosci. Glycobiol.}, Volume = {10}, Pages = {349-404}, year = 1999 } @Article{BHW+99b, Author = {Bouckaert, J and Hamelryck, TW and Wyns, L and Loris, R}, Title = {The crystal structures of {M}an(alpha1-3){M}an(alpha1-{O}){M}e and {M}an(alpha1-6){M}an(alpha1-{O}){M}e in complex with concanavalin {A}.}, Journal = {J Biol Chem}, Volume = {274}, Pages = {29188-95}, abstract = {The crystal structures of concanavalin A in complex with Man(alpha1-6)Man(alpha1-O)Me and Man(alpha1-3)Man(alpha1-O)Me were determined at resolutions of 2.0 and 2.8 A, respectively. In both structures, the O-1-linked mannose binds in the conserved monosaccharide-binding site. The O-3-linked mannose of Man(alpha1-3)Man(alpha1-O)Me binds in the hydrophobic subsite formed by Tyr-12, Tyr-100, and Leu-99. The shielding of a hydrophobic surface is consistent with the associated large heat capacity change. The O-6-linked mannose of Man(alpha1-6)Man(alpha1-O)Me binds in the same subsite formed by Tyr-12 and Asp-16 as the reducing mannose of the highly specific trimannose Man(alpha1-3)[Man(alpha1-6)]Man(alpha1-O)Me. However, it is much less tightly bound. Its O-2 hydroxyl makes no hydrogen bond with the conserved water 1. Water 1 is present in all the sugar-containing concanavalin A structures and increases the complementarity between the protein-binding surface and the sugar, but is not necessarily a hydrogen-bonding partner. A water analysis of the carbohydrate-binding site revealed a conserved water molecule replacing O-4 on the alpha1-3-linked arm of the trimannose. No such water is found for the reducing or O-6-linked mannose. Our data indicate that the central mannose of Man(alpha1-3)[Man(alpha1-6)]Man(alpha1-O)Me primarily functions as a hinge between the two outer subsites.}, authoraddress = {Laboratorium voor Ultrastructuur, Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel, Paardenstraat 65, B-1640 Sint-Genesius-Rode, Belgium. bouckaej@vub.ac.be}, country = {UNITED STATES}, keywords = {Binding Sites ; Carbohydrate Conformation ; Concanavalin A/*chemistry ; Crystallography, X-Ray ; Disaccharides/*chemistry ; Mannosides/*chemistry ; Models, Molecular ; Protein Binding ; Support, Non-U.S. Gov't ; Thermodynamics ; Water/chemistry}, language = {eng}, medline-da = {19991109}, medline-dcom = {19991109}, medline-edat = {1999/10/03 09:00}, medline-is = {0021-9258}, medline-jc = {HIV}, medline-jid = {2985121R}, medline-lr = {20001218}, medline-mhda = {1999/10/03 09:00}, medline-pmid = {10506175}, medline-pst = {ppublish}, medline-pt = {Journal Article}, medline-rn = {0 (Disaccharides) ; 0 (Mannosides) ; 11028-71-0 (Concanavalin A) ; 7732-18-5 (Water)}, medline-sb = {IM}, medline-si = {PDB/1QDC ; PDB/1QDO}, medline-so = {J Biol Chem 1999 Oct 8;274(41):29188-95.}, medline-urlf = {http://www.jbc.org/cgi/content/full/274/41/29188}, medline-urls = {http://www.jbc.org/cgi/content/abstract/274/41/29188}, medlineref = {99436125}, year = 1999 } @Article{BHW+99, Author = {Bouckaert, J and Hamelryck, T and Wyns, L and Loris, R}, Title = {Novel structures of plant lectins and their complexes with carbohydrates.}, Journal = {Curr Opin Struct Biol}, Volume = {9}, Pages = {572-7}, abstract = {Several novel structures of legume lectins have led to a thorough understanding of monosaccharide and oligosaccharide specificity, to the determination of novel and surprising quaternary structures and, most importantly, to the structural identification of the binding site for adenine and plant hormones. This deepening of our understanding of the structure/function relationships among the legume lectins is paralleled by advances in two other plant lectin families - the monocot lectins and the jacalin family. As the number of available crystal structures increases, more parallels between plant and animal lectins become apparent.}, authoraddress = {Laboratorium voor Ultrastruktuur, Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel, Paardenstraat 65, B-1640, Sint-Genesius-Rode, Belgium.}, country = {ENGLAND}, keywords = {Binding Sites ; Carbohydrates/*chemistry ; Dimerization ; Lectins/*chemistry ; Macromolecular Systems ; Models, Molecular ; Plant Growth Regulators/chemistry ; Plants ; Protein Conformation ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Support, Non-U.S. Gov't}, language = {eng}, medline-aid = {sb9502 [pii]}, medline-da = {19991105}, medline-dcom = {19991105}, medline-edat = {1999/10/06 09:00}, medline-is = {0959-440X}, medline-jc = {B9V}, medline-jid = {9107784}, medline-lr = {20001218}, medline-mhda = {1999/10/06 09:00}, medline-pmid = {10508764}, medline-pst = {ppublish}, medline-pt = {Journal Article ; Review ; Review, Tutorial}, medline-rf = {34}, medline-rn = {0 (Carbohydrates) ; 0 (Lectins) ; 0 (Macromolecular Systems) ; 0 (Plant Growth Regulators)}, medline-sb = {IM}, medline-so = {Curr Opin Struct Biol 1999 Oct;9(5):572-7.}, medline-urlf = {http://www.biomednet.com/article/sb9502}, medlineref = {99439921}, year = 1999 } @Article{HLB+99b, Author = {Hamelryck, TW and Loris, R and Bouckaert, J and Dao-Thi, MH and Strecker, G and Imberty, A and Fernandez, E and Wyns, L and Etzler, ME}, Title = {Carbohydrate binding, quaternary structure and a novel hydrophobic binding site in two legume lectin oligomers from {D}olichos biflorus.}, Journal = {J Mol Biol}, Volume = {286}, Pages = {1161-77}, abstract = {The seed lectin (DBL) from the leguminous plant Dolichos biflorus has a unique specificity among the members of the legume lectin family because of its high preference for GalNAc over Gal. In addition, precipitation of blood group A+H substance by DBL is slightly better inhibited by a blood group A trisaccharide (GalNAc(alpha1-3)[Fuc(alpha1-2)]Gal) containing pentasaccharide, and about 40 times better by the Forssman disaccharide (GalNAc(alpha1-3)GalNAc) than by GalNAc. We report the crystal structures of the DBL-blood group A trisaccharide complex and the DBL-Forssman disaccharide complex.A comparison with the binding sites of Gal-binding legume lectins indicates that the low affinity of DBL for Gal is due to the substitution of a conserved aromatic residue by an aliphatic residue (Leu127). Binding studies with a Leu127Phe mutant corroborate these conclusions. DBL has a higher affinity for GalNAc because the N-acetyl group compensates for the loss of aromatic stacking in DBL by making a hydrogen bond with the backbone amide group of Gly103 and a hydrophobic contact with the side-chains of Trp132 and Tyr104.Some legume lectins possess a hydrophobic binding site that binds adenine and adenine-derived plant hormones, i.e. cytokinins. The exact function of this binding site is unknown, but adenine/cytokinin-binding legume lectins might be involved in storage of plant hormones or plant growth regulation. The structures of DBL in complex with adenine and of the dimeric stem and leaf lectin (DB58) from the same plant provide the first structural data on these binding sites. Both oligomers possess an unusual architecture, featuring an alpha-helix sandwiched between two monomers. In both oligomers, this alpha-helix is directly involved in the formation of the hydrophobic binding site. DB58 adopts a novel quaternary structure, related to the quaternary structure of the DBL heterotetramer, and brings the number of know legume lectin dimer types to four.}, authoraddress = {Laboratorium voor Ultrastructuur, Vlaams Interuniversitair Instituur voor Biotechnologie, Vrije Universiteit Brussel, Paardenstraat 65, Sint-Genesius-Rode, B-1640, Belgium. thamelry@vub.ac.be}, country = {ENGLAND}, keywords = {Adenine/metabolism ; Binding Sites ; Carbohydrates/*metabolism ; Crystallography, X-Ray ; Forssman Antigen/metabolism ; Lectins/*chemistry/genetics ; Models, Molecular ; Mutagenesis, Site-Directed ; Oligosaccharides/*chemistry/metabolism ; Protein Conformation ; Rosales/chemistry ; Substrate Specificity ; Support, Non-U.S. Gov't ; Support, U.S. Gov't, P.H.S.}, language = {eng}, medline-ci = {Copyright 1999 Academic Press.}, medline-da = {19990415}, medline-dcom = {19990415}, medline-edat = {1999/02/27 03:13}, medline-ein = {J Mol Biol 1999 May 21;288(5):1037}, medline-id = {GM21882/GM/NIGMS}, medline-is = {0022-2836}, medline-jc = {J6V}, medline-jid = {2985088R}, medline-lr = {20001218}, medline-mhda = {1999/02/27 03:13}, medline-pmid = {10047489}, medline-pst = {ppublish}, medline-pt = {Journal Article}, medline-rn = {0 (Carbohydrates) ; 0 (DB58 lectin, Dolichos biflorus) ; 0 (Lectins) ; 0 (Oligosaccharides) ; 0 (blood group A trisaccharide) ; 73-24-5 (Adenine) ; 9013-60-9 (Forssman Antigen)}, medline-sb = {IM}, medline-so = {J Mol Biol 1999 Mar 5;286(4):1161-77.}, medlineref = {99158818}, year = 1999 } @Article{HMC+00, Author = {Hamelryck, TW and Moore, JG and Chrispeels, MJ and Loris, R and Wyns, L}, Title = {The role of weak protein-protein interactions in multivalent lectin-carbohydrate binding: crystal structure of cross-linked {FRIL}.}, Journal = {J Mol Biol}, Volume = {299}, Pages = {875-83}, abstract = {Binding of multivalent glycoconjugates by lectins often leads to the formation of cross-linked complexes. Type I cross-links, which are one-dimensional, are formed by a divalent lectin and a divalent glycoconjugate. Type II cross-links, which are two or three-dimensional, occur when a lectin or glycoconjugate has a valence greater than two. Type II complexes are a source of additional specificity, since homogeneous type II complexes are formed in the presence of mixtures of lectins and glycoconjugates. This additional specificity is thought to become important when a lectin interacts with clusters of glycoconjugates, e.g. as is present on the cell surface. The cryst1al structure of the Glc/Man binding legume lectin FRIL in complex with a trisaccharide provides a molecular snapshot of how weak protein-protein interactions, which are not observed in solution, can become important when a cross-linked complex is formed. In solution, FRIL is a divalent dimer, but in the crystal FRIL forms a tetramer, which allows for the formation of an intricate type II cross-linked complex with the divalent trisaccharide. The dependence on weak protein-protein interactions can ensure that a specific type II cross-linked complex and its associated specificity can occur only under stringent conditions, which explains why lectins are often found forming higher-order oligomers.}, authoraddress = {Laboratorium voor Ultrastructuur, Vlaams Interuniversitair Instituut voor Biotechnologie, Vrije Universiteit Brussel, Paardenstraat 65, Sint-Genesius-Rode, B-1640, Belgium. thamelry@vub.ac.be}, country = {ENGLAND}, keywords = {Binding Sites ; Carbohydrate Conformation ; Carbohydrate Sequence ; Concanavalin A/chemistry/metabolism ; Cross-Linking Reagents/chemistry/*metabolism ; Crystallography, X-Ray ; Dimerization ; Hydrogen Bonding ; Lectins/*chemistry/*metabolism ; Legumes/*chemistry ; Mannose/chemistry/metabolism ; Models, Molecular ; Molecular Sequence Data ; Protein Binding ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Substrate Specificity ; Support, Non-U.S. Gov't ; Trisaccharides/chemistry/*metabolism}, language = {eng}, medline-aid = {10.1006/jmbi.2000.3785 [doi] ; jmbi.2000.3785 [pii]}, medline-ci = {Copyright 2000 Academic Press.}, medline-da = {20000712}, medline-dcom = {20000712}, medline-edat = {2000/06/14 09:00}, medline-is = {0022-2836}, medline-jc = {J6V}, medline-jid = {2985088R}, medline-lr = {20001218}, medline-mhda = {2000/07/15 11:00}, medline-pmid = {10843844}, medline-pst = {ppublish}, medline-pt = {Journal Article}, medline-rn = {0 (Cross-Linking Reagents) ; 0 (FRIL protein) ; 0 (Lectins) ; 0 (Trisaccharides) ; 11028-71-0 (Concanavalin A) ; 31103-86-3 (Mannose)}, medline-sb = {IM}, medline-si = {PDB/1QMO ; PDB/R1QMOSF}, medline-so = {J Mol Biol 2000 Jun 16;299(4):875-83.}, medlineref = {20304887}, year = 2000 } @Misc{HK01, Author = {Hamelryck, T. and Kjeldgaard, M.}, Title = {An open source multi-purpose programming environment for macromolecular crystallography}, HowPublished = {CCP4 newsletter on protein crystallography, Nr. 39}, year = 2001 } @Article{BDL+01, Author = {Buts, L and Dao-Thi, MH and Loris, R and Wyns, L and Etzler, M and Hamelryck, T}, Title = {Weak protein-protein interactions in lectins: the crystal structure of a vegetative lectin from the legume {D}olichos biflorus.}, Journal = {J Mol Biol}, Volume = {309}, Pages = {193-201}, abstract = {The legume lectins are widely used as a model system for studying protein-carbohydrate and protein-protein interactions. They exhibit a fascinating quaternary structure variation, which becomes important when they interact with multivalent glycoconjugates, for instance those on cell surfaces. Recently, it has become clear that certain lectins form weakly associated oligomers. This phenomenon may play a role in the regulation of receptor crosslinking and subsequent signal transduction. The crystal structure of DB58, a dimeric lectin from the legume Dolichos biflorus reveals a separate dimer of a previously unobserved type, in addition to a tetramer consisting of two such dimers. This tetramer resembles that formed by DBL, the seed lectin from the same plant. A single amino acid substitution in DB58 affects the conformation and flexibility of a loop in the canonical dimer interface. This disrupts the formation of a stable DBL-like tetramer in solution, but does not prohibit its formation in suitable conditions, which greatly increases the possibilities for the cross-linking of multivalent ligands. The non-canonical DB58 dimer has a buried symmetrical alpha helix, which can be present in the crystal in either of two antiparallel orientations. Two existing structures and datasets for lectins with similar quaternary structures were reconsidered. A central alpha helix could be observed in the soybean lectin, but not in the leucoagglutinating lectin from Phaseolus vulgaris. The relative position and orientation of the carbohydrate-binding sites in the DB58 dimer may affect its ability to crosslink mulitivalent ligands, compared to the other legume lectin dimers.}, authoraddress = {ULTR-Ultrastructure Department, Vrije Universiteit Brussel, Sint-Genesius-Rode Belgium. lieven@ultr.vub.ac.be}, country = {England}, keywords = {Amino Acid Sequence ; Amino Acid Substitution/genetics ; Binding Sites ; Carbohydrates/metabolism ; Crystallography, X-Ray ; Dimerization ; Lectins/*chemistry/genetics/*metabolism ; Legumes/*chemistry/genetics ; Ligands ; Models, Molecular ; Molecular Sequence Data ; Protein Binding ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Sequence Alignment ; Structure-Activity Relationship ; Support, Non-U.S. Gov't}, language = {eng}, medline-da = {20010808}, medline-dcom = {20010816}, medline-edat = {2001/08/09 10:00}, medline-is = {0022-2836}, medline-jc = {J6V}, medline-jid = {2985088R}, medline-mhda = {2001/08/17 10:01}, medline-pmid = {11491289}, medline-pst = {ppublish}, medline-pt = {Journal Article}, medline-rn = {0 (Carbohydrates) ; 0 (Lectins) ; 0 (Ligands)}, medline-sb = {IM}, medline-si = {PDB/1AX0 ; PDB/1DBN ; PDB/1G7Y ; PDB/1G8W ; PDB/1G9F ; PDB/1GSL ; PDB/1LU1 ; PDB/1LU2 ; PDB/1QMO ; PDB/1QNW ; PDB/1WBL ; PDB/R1G7YSF ; PDB/R1G8WSF ; PDB/R1G9FSF}, medline-so = {J Mol Biol 2001 May 25;309(1):193-201.}, medlineref = {21383379}, year = 2001 } @Article{Ham03, Author = {Hamelryck, T.}, Title = {Efficient identification of side-chain patterns using a multidimensional index tree.}, Journal = {Proteins}, Volume = {51}, Pages = {96-108}, abstract = {Convergent evolution often produces similar functional sites in nonhomologous proteins. The identification of these sites can make it possible to infer function from structure, to pinpoint the location of a functional site, to identify enzymes with similar enzymatic mechanisms, or to discover putative functional sites. In this article, a novel method is presented that (a) queries a database of protein structures for the occurrence of a given side chain pattern and (b) identifies interesting side-chain patterns in a given structure. For efficiency and to make a robust statistical evaluation of the significance of a similarity possible, patterns of three residues (or triads) are considered. Each triad is encoded as a high-dimensional vector and stored in an SR (Sphere/Rectangle) tree, an efficient multidimensional index tree. Identifying similar triads can then be reformulated as identifying neighboring vectors. The method deals with many features that otherwise complicate the identification of meaningful patterns: shifted backbone positions, conservative substitutions, various atom label ambiguities and mirror imaged geometries. The combined treatment of these features leads to the identification of previously unidentified patterns. In particular, the identification of mirror imaged side-chain patterns is unique to the here-described method. Interesting triads in a given structure can be identified by extracting all triads and comparing them with a database of triads involved in ligand binding. The approach was tested by an all-against-all comparison of unique representatives of all SCOP superfamilies. New findings include mirror imaged metal binding and active sites, and a putative active site in bacterial luciferase.}, authoraddress = {ULTR Department, Vrije Universiteit Brussel (VUB), Vlaams Interuniversitair Instituut voor Biotechnologie (VIB), Brussel, Belgium. thamelry@vub.ac.be}, keywords = {6-Phytase/chemistry ; Alcohol Oxidoreductases/chemistry ; Amino Acid Sequence ; Amino Acids/chemistry ; Bacteria/enzymology ; Binding Sites ; Catalytic Domain ; Enzymes/*chemistry/metabolism ; Hydrolases/chemistry ; Ligands ; Luciferase/chemistry/metabolism ; Metals/metabolism ; Models, Molecular ; Pancreatic Elastase/chemistry ; Phenylalanine Hydroxylase/chemistry ; Pyrophosphatases/chemistry ; Sequence Analysis, Protein/*methods}, language = {eng}, medline-aid = {10.1002/prot.10338 [doi]}, medline-ci = {Copyright 2003 Wiley-Liss, Inc.}, medline-da = {20030221}, medline-dcom = {20030409}, medline-edat = {2003/02/22 04:00}, medline-fau = {Hamelryck, Thomas}, medline-is = {1097-0134}, medline-jid = {8700181}, medline-mhda = {2003/04/10 05:00}, medline-own = {nlm}, medline-pl = {United States}, medline-pmid = {12596267}, medline-pst = {ppublish}, medline-pt = {Evaluation Studies ; Journal Article}, medline-rn = {0 (Amino Acids) ; 0 (Enzymes) ; 0 (Ligands) ; 0 (Metals) ; EC 1.1 (Alcohol Oxidoreductases) ; EC 1.1.1.85 (3-isopropylmalate dehydrogenase) ; EC 1.13.12.- (Luciferase) ; EC 1.14.16.1 (Phenylalanine Hydroxylase) ; EC 3. (Hydrolases) ; EC 3.1.3.26 (6-Phytase) ; EC 3.4.21.36 (Pancreatic Elastase) ; EC 3.6.1.- (Pyrophosphatases) ; EC 3.7.1.2 (fumarylacetoacetase)}, medline-sb = {IM}, medline-so = {Proteins 2003 Apr 1;51(1):96-108.}, medline-stat = {completed}, medlineref = {22484206}, year = 2003 } @Article{HM03, Author = {Hamelryck, T. and Manderick, B.}, Title = {P{DB} file parser and structure class implemented in {P}ython.}, Journal = {Bioinformatics}, Volume = {19}, Pages = {2308-10}, abstract = {The biopython project provides a set of bioinformatics tools implemented in Python. Recently, biopython was extended with a set of modules that deal with macromolecular structure. Biopython now contains a parser for PDB files that makes the atomic information available in an easy-to-use but powerful data structure. The parser and data structure deal with features that are often left out or handled inadequately by other packages, e.g. atom and residue disorder (if point mutants are present in the crystal), anisotropic B factors, multiple models and insertion codes. In addition, the parser performs some sanity checking to detect obvious errors. AVAILABILITY: The Biopython distribution (including source code and documentation) is freely available (under the Biopython license) from http://www.biopython.org}, authoraddress = {Department of Cellular and Molecular Interactions, Vlaams Interuniversitair Instituut voor Biotechnologie and Computational Modeling Lab, Department of Computer Science, Vrije Universiteit Brussel, Pleinlaan 2, 1050 Brussels, Belgium. thamelry@vub.ac.be}, language = {eng}, medline-da = {20031121}, medline-edat = {2003/11/25 05:00}, medline-fau = {Hamelryck, Thomas ; Manderick, Bernard}, medline-is = {1367-4803}, medline-jid = {9808944}, medline-mhda = {2003/11/25 05:00}, medline-own = {NLM}, medline-pl = {England}, medline-pmid = {14630660}, medline-pst = {ppublish}, medline-pt = {Journal Article}, medline-sb = {IM}, medline-so = {Bioinformatics 2003 Nov 22;19(17):2308-10.}, medline-stat = {in-process}, year = 2003 } @Article{Ham05, Author = {Hamelryck, T.}, Title = {An amino acid has two sides: a new 2{D} measure provides a different view of solvent exposure.}, Journal = {Proteins}, Volume = {59}, Pages = {38-48}, abstract = {The concept of amino acid solvent exposure is crucial for understanding and predicting various aspects of protein structure and function. The traditional measures of solvent exposure however suffer from various shortcomings, like for example the inability to distinguish exposed, partly exposed, buried, and deeply buried residues. This article introduces a new measure of solvent exposure called Half-Sphere Exposure that addresses many of the shortcomings of other methods. The new measure outperforms other measures with respect to correlation with protein stability, conservation among fold homologs, amino acid-type dependency and interpretation. The measure consists of the number of Calpha atoms in two half spheres around a residue's Calpha atom. Conceptually, one of the half spheres corresponds to the side chain's neighborhood, the other half sphere being in the opposite direction. We show here that the two half spheres correspond to two regions around an amino acid that are surprisingly distinct in terms of geometry and energy. This aspect of protein structure introduced here forms the basis of the Half-Sphere Exposure measure. The results strongly suggest that in many respects, a 2D measure is inherently much better suited to describe solvent exposure than the traditional 1D measures. Importantly, Half-Sphere Exposure can be calculated from the Calpha atom coordinates only, which abolishes the need for a full-atom model to calculate solvent exposure. Hence, the measure can be used in protein structure prediction methods that are based on various simplified models. Half-Sphere Exposure has great potential for use in protein structure prediction and analysis.}, authoraddress = {Bioinformatics Center, University of Copenhagen, Copenhagen, Denmark. thamelry@binf.ku.dk }, language = {eng}, medline-aid = {10.1002/prot.20379 [doi]}, medline-ci = {(c) 2005 Wiley-Liss, Inc.}, medline-da = {20050302}, medline-edat = {2005/02/03 09:00}, medline-fau = {Hamelryck, Thomas}, medline-is = {1097-0134}, medline-jid = {8700181}, medline-mhda = {2005/02/03 09:00}, medline-own = {NLM}, medline-pl = {United States}, medline-pmid = {15688434}, medline-pst = {ppublish}, medline-pt = {Journal Article}, medline-pubm = {Print}, medline-sb = {IM}, medline-so = {Proteins 2005 Apr 1;59(1):38-48.}, medline-stat = {In-Process}, year = 2005 } @Article{BH05, Author = {Boomsma, W. and Hamelryck, T.}, Title = {Full {C}yclic {C}oordinate {D}escent: {S}olving {T}he {P}rotein {L}oop {C}losure {P}roblem {I}n {C}alpha {S}pace.}, Journal = {BMC Bioinformatics}, Volume = {6}, Number = {1}, Pages = {159}, abstract = {BACKGROUND: Various forms of the so-called loop closure problem are crucial to protein structure prediction methods. Given an N- and a C-terminal end, the problem consists of finding a suitable segment of a certain length that bridges the ends seamlessly. In homology modelling, the problem arises in predicting loop regions. In de novo protein structure prediction, the problem is encountered when implementing local moves for Markov Chain Monte Carlo simulations. Most loop closure algorithms keep the bond angles fixed or semi-fixed, and only vary the dihedral angles. This is appropriate for a full-atom protein backbone, since the bond angles can be considered as fixed, while the (theta,tau) dihedral angles are variable. However, many de novo structure prediction methods use protein models that only consist of Calpha atoms, or otherwise do not make use of all backbone atoms. These methods require a method that alters both bond and dihedral angles, since the pseudo bond angle between three consecutive Calpha atoms also varies considerably. RESULTS: Here we present a method that solves the loop closure problem for Calpha only protein models. We developed a variant of Cyclic Coordinate Descent (CCD), an inverse kinematics method from the field of robotics, which was recently applied to the loop closure problem. Since the method alters both bond and dihedral angles, which is equivalent to applying a full rotation matrix, we call our method Full CCD (FCDD). FCCD replaces CCD's vector-based optimization of a rotation around an axis with a singular value decomposition-based optimization of a general rotation matrix. The method is easy to implement and numerically stable. CONCLUSIONS: We tested the method's performance on sets of random protein Calpha segments between 5 and 30 amino acids long, and a number of loops of length 4, 8 and 12. FCCD is fast, has a high success rate and readily generates conformations close to those of real loops. The presence of constraints on the angles only has a small effect on the performance. A reference implementation of FCCD in Python is available as supplementary information.}, language = {ENG}, medline-aid = {1471-2105-6-159 [pii] ; 10.1186/1471-2105-6-159 [doi]}, medline-da = {20050629}, medline-dep = {20050628}, medline-edat = {2005/06/30 09:00}, medline-is = {1471-2105}, medline-jid = {100965194}, medline-mhda = {2005/06/30 09:00}, medline-own = {NLM}, medline-phst = {2005/04/25 [received] ; 2005/06/28 [accepted] ; 2005/06/28 [aheadofprint]}, medline-pmid = {15985178}, medline-pst = {aheadofprint}, medline-pt = {JOURNAL ARTICLE}, medline-pubm = {Print-Electronic}, medline-so = {BMC Bioinformatics 2005 Jun 28;6(1):159.}, medline-stat = {Publisher}, year = 2005 } @InProceedings{FB505, Author = {Kent, JT and Hamelryck, T.}, Title = {Using the {F}isher-{B}ingham distribution in stochastic models for protein structure.}, BookTitle = {Quantitative Biology, Shape Analysis, and Wavelets}, Editor = {Barber, S. and Baxter, PD. and Mardia, KV. and Walls, RE.}, Volume = {24}, Pages = {57-60}, Publisher = {Leeds University Press}, year = 2005 } @InProceedings{Lasr2006, Author = {Boomsma, W. and Kent, JT. and Mardia, KV. and Taylor, CC. and Hamelryck, T.}, Title = {Graphical models and directional statistics capture protein structure}, BookTitle = {Interdisciplinary Statistics and Bioinformatics}, Editor = {Barber, S. and Baxter, PD. and Mardia, KV. and Walls, RE.}, Volume = {25}, Pages = {91-94}, Publisher = {Leeds University Press}, year = 2006 } @article{HKK06, Author = {Hamelryck, T. and Kent, JT. and Krogh, A.}, Title = {Sampling realistic protein conformations using local structural bias}, Journal = {PLoS Comp. Biol.}, Volume = {2}, Number = {9}, Pages = {e131}, year = {2006} } @article{Torus08, Author = {Boomsma, W. and Mardia, KV. and Taylor, CC. and Ferkinghoff-Borg, J. and Krogh, A. and Hamelryck, T.}, Title = {A generative, probabilistic model of local protein structure.}, Journal = {Proc. Natl. Acad. USA}, Volume = {105}, Pages = {8932--8937}, year = {2008} } @article{Crisp, Author = {Boomsma, W. and Bottaro, S. and Hamelryck, T. and Ferkinghoff-Borg, J. }, Title = {Dramatic speed-up of molecular simulations using local moves guided by a probabilistic model.}, volume = {In preparation}, year = {2009} } @InProceedings{CASP08, author={Boomsma, W. and Borg, M. and Frellsen, J. and Harder, T. and Stovgaard, K. and Ferkinghoff-Borg, J. and Krogh, A. and Mardia, KV. and Hamelryck, T.}, year = {2008}, title = {{PHAISTOS: protein structure prediction using a probabilistic model of local structure.}}, booktitle={{Proceedings of CASP8}}, address = {{Cagliari, Sardinia, Italy}}, month = {December 3-7}, pages = {82-83} } @InProceedings{PHAISTOS_LASR09, author={Borg, M. and Mardia, KV. and Boomsma, W. and Frellsen, J. and Harder, T. and Stovgaard, K. and Ferkinghoff-Borg, J. and Røgen, P. and Hamelryck, T.}, title={{A probabilistic approach to protein structure prediction: PHAISTOS in CASP9}}, year={2009}, booktitle={{LASR2009 - Statistical tools for challenges in bioinformatics}}, editor={Gusnanto, A. and Mardia, KV. and Fallaize, CJ.}, pages={65--70}, publisher={Leeds University Press, Leeds, UK} } @article{SMMR09, author = {Hamelryck, T.}, title = {Probabilistic models and machine learning in structural bioinformatics}, journal = {Stat. Meth. Med. Res.}, year = {2009}, volume = {18}, pages={505--526} } @article{Barnacle09, author={Frellsen, J. and Moltke, I. and Thiim, M. and Mardia, KV. and Ferkinghoff-Borg, J. and Hamelryck, T.}, year={2009}, title={A probabilistic model of {RNA} conformational space}, journal={PLoS Comp. Biol.}, volume={5}, pages={e1000406} } @article{Mocapy2010, author={Paluszewski, M. and Hamelryck, T.}, year={2010}, title={{Mocapy++ - A toolkit for inference and learning in dynamic Bayesian networks}}, journal={BMC Bioinformatics}, volume={11}, pages={126} } @article{biopython2009, title={{Biopython: freely available Python tools for computational molecular biology and bioinformatics}}, author={Cock, P.J.A. and Antao, T. and Chang, J.T. and Chapman, B.A. and Cox, C.J. and Dalke, A. and Friedberg, I. and Hamelryck, T. and Kauff, F. and Wilczynski, B. and others}, journal={Bioinformatics}, volume={25}, pages={1422--1423}, year={2009}, } @article{harder2010beyond, title={{Beyond rotamers: a generative, probabilistic model of side chains in proteins}}, author={Harder, T. and Boomsma, W. and Paluszewski, M. and Frellsen, J. and Johansson, K. and Hamelryck, T.}, journal={BMC bioinformatics}, volume={11}, pages={306}, year={2010}, }