Structural model for family 32 of glycosyl-hydrolase enzymes (original) (raw)
Related papers
2000
Type I1 antifreeze proteins (AFP), which inhibit the growth of seed ice crystals in the blood of certain fishes (sea raven, herring, and smelt), are the largest known fish AFPs and the only class for which detailed structural information is not yet available. However, a sequence homology has been recognized between these proteins and the carbohydrate recognition domain of C-type lectins. The structure of this domain from rat mannose-binding protein (MBP-A) has been solved by X-ray crystallography (Weis WI, Drickamer K, Hendrickson WA, 1992, Nature 360:127-134) and provided the coordinates for constructing the three-dimensional model of the 129-amino acid Type I1 AFP from sea raven, to which it shows 19% sequence identity. Multiple sequence alignments between Type I1 AFPs, pancreatic stone protein, MBP-A, and as many as 50 carbohydrate-recognition domain sequences from various lectins were performed to determine reliably aligned sequence regions. Successive molecular dynamics and energy minimization calculations were used to relax bond lengths and angles and to identify flexible regions. The derived structure contains two a-helices, two o-sheets, and a high proportion of amino acids in loops and turns. The model is in good agreement with preliminary NMR spectroscopic analyses. It explains the observed differences in calcium binding between sea raven Type I1 AFP and MBP-A. Furthermore, the model proposes the formation of five disulfide bridges between Cys 7 and Cys 18, Cys 35 and Cys 125, Cys 69 and Cys 100, Cys 89 and Cys 11 1, and Cys 101 and Cys 117. Based on the predicted features of this model, a site for proteinice interaction is proposed.
Comparative modeling of the three‐dimensional structures of family 3 glycoside hydrolases
Proteins: Structure, …, 2000
Type I1 antifreeze proteins (AFP), which inhibit the growth of seed ice crystals in the blood of certain fishes (sea raven, herring, and smelt), are the largest known fish AFPs and the only class for which detailed structural information is not yet available. However, a sequence homology has been recognized between these proteins and the carbohydrate recognition domain of C-type lectins. The structure of this domain from rat mannose-binding protein (MBP-A) has been solved by X-ray crystallography (Weis WI, Drickamer K, Hendrickson WA, 1992, Nature 360:127-134) and provided the coordinates for constructing the three-dimensional model of the 129-amino acid Type I1 AFP from sea raven, to which it shows 19% sequence identity. Multiple sequence alignments between Type I1 AFPs, pancreatic stone protein, MBP-A, and as many as 50 carbohydrate-recognition domain sequences from various lectins were performed to determine reliably aligned sequence regions. Successive molecular dynamics and energy minimization calculations were used to relax bond lengths and angles and to identify flexible regions. The derived structure contains two a-helices, two o-sheets, and a high proportion of amino acids in loops and turns. The model is in good agreement with preliminary NMR spectroscopic analyses. It explains the observed differences in calcium binding between sea raven Type I1 AFP and MBP-A. Furthermore, the model proposes the formation of five disulfide bridges between Cys 7 and Cys 18, Cys 35 and Cys 125, Cys 69 and Cys 100, Cys 89 and Cys 11 1, and Cys 101 and Cys 117. Based on the predicted features of this model, a site for proteinice interaction is proposed.
Methods, 2016
Thousands of protein structures of unknown or uncertain function have been reported as a result of high-throughput structure determination techniques developed by Structural Genomics (SG) projects. However, many of the putative functional assignments of these SG proteins in the Protein Data Bank (PDB) are incorrect. While high-throughput biochemical screening techniques have provided valuable functional information for limited sets of SG proteins, the biochemical functions for most SG proteins are still unknown or uncertain. Therefore, computational methods for the reliable prediction of protein function from structure can add tremendous value to the existing SG data. In this article, we show how computational methods may be used to predict the function of SG proteins, using examples from the six-hairpin glycosidase (6-HG) and the concanavalin Alike lectins/glucanases (CAL/G) superfamilies. Using a set of predicted functional residues, obtained from computed electrostatic and chemical properties for each protein structure, it is shown that these superfamilies may be sorted into functional families according to biochemical function. Within these superfamilies, a total of 18 SG proteins were analyzed according to their predicted, local functional sites: 13 from the 6-HG superfamily, five from the CAL/G superfamily. Within the 6-HG superfamily, an uncharacterized protein bacova_03626 from Bacteroides ovatus (PDB 3ON6) and a hypothetical protein BT3781 from Bacteroides thetaiotaomicron (PDB 2P0V) are shown to have very strong active site matches with exo-α-1,6-mannosidases, thus likely possessing this function. Also in this superfamily, it is shown that protein BH0842, a putative glycoside hydrolase from Bacteroides halodurans (PDB 2RDY), has a predicted active site that matches well with a known α-L-galactosidase. In the CAL/G superfamily, an uncharacterized glycosyl hydrolase family 16 protein from Mycobacterium smegmatis (PDB 3RQ0) is shown to have local structural similarity at the predicted active site with the known members of the GH16 family, with the closest match to the endoglucanase subfamily. The method discussed herein can predict whether an SG protein is correctly or incorrectly annotated and can sometimes provide a reliable functional annotation. Examples of application of the method across folds, comparing active sites between two proteins of different structural folds, are also given.
A computational approach to structural properties of glycoside hydrolase family 4 from bacteria
Acta biochimica Polonica, 2013
Structural bioinformatics approaches applied to the alpha- and beta-glycosidases from the GH4 enzyme family reveal that, despite low sequence identity, these enzymes possess quite similar global structural characteristics reflecting a common reaction mechanism. Locally, there are a few distinctive structural characteristics of GH4 alpha- and beta-glycosidases, namely, surface cavities with different geometric characteristics and two regions with highly dissimilar structural organizations and distinct physicochemical properties in the alpha- and beta-glucosidases from Thermotoga maritima. We suggest that these structurally dissimilar regions may be involved in specific protein-protein interactions and this hypothesis is sustained by the predicted distinct functional partners of the investigated proteins. Also, we predict that alpha- and beta-glycosidases from the GH4 enzyme family interact with difenoconazole, a fungicide, but there are different features of these interactions especi...
Proteins: Structure, Function, and Bioinformatics, 2004
Multiple-sequence alignment of glycoside hydrolase (GH) families 32, 43, 62, and 68 revealed three conserved blocks, each containing an acidic residue at an equivalent position in all the enzymes. A detailed analysis of the site-directed mutations so far performed on invertases (GH32), arabinanases (GH43), and bacterial fructosyltransferases (GH68) indicated a direct implication of the conserved residues Asp/Glu (block I), Asp (block II), and Glu (block III) in substrate binding and hydrolysis. These residues are close in space in the 5-bladed -propeller fold determined for Cellvibrio japonicus ␣-L-arabinanase Arb43A [Nurizzo et al., Nat Struct Biol 2002;9:665-668] and Bacillus subtilis endo-1,5-␣-L-arabinanase. A sequence-structure compatibility search using 3D-PSSM, mGenTHREADER, INBGU, and SAM-T02 programs predicted indistinctly the 5-bladed -propeller fold of Arb43A and the 6-bladed -propeller fold of sialidase/neuraminidase (GH33, GH34
FEBS Letters, 2002
X-ray crystallography and bioinformatics studies reveal a tendency for the right-handed L L-helix domain architecture to be associated with carbohydrate binding proteins. Here we demonstrate the presence of catalytic L L-helix domains in glycoside hydrolase (GH) families 49, 55 and 87 and provide evidence for their sharing a common evolutionary ancestor with two structurally characterized GH families, numbers 28 and 82. This domain assignment helps assign catalytic residues to each family. Further analysis of domain architecture reveals the association of carbohydrate binding modules with catalytic GH L L-helices, as well as an unexpected pair of L L-helix domains in GH family 55. ß 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.
Mireia Comellas-Bigler et al., Structure, 10, 865-876 (2002)
2015
Bacillus coagulans (J-4) [5], which share between 30% and Wolfram Bode 1,5 and 35% sequence identity. This proteinase family is not 1 Abteilung fü r Strukturforschung restricted to prokaryotes, but also includes eukaryotic Max-Planck-Institut fü r Biochemie homologs, and quite recently, the human lysosomal tri-Am Klopferspitz 18 a peptidyl-peptidase I (also termed CLN2) has been as-
Molecular modeling of family GH16 glycoside hydrolases: Potential
Citeseer
Family GH16 glycoside hydrolases can be assigned to five subgroups according to their substrate specificities, including xyloglucan transglucosylases/hydrolases (XTHs), (1,3)--galactanases, (1,4)--galactanases/-carrageenases, "nonspecific" (1,3/1,3;1,4)--D-glucan endohydrolases, and (1,3;1,4)--D-glucan endohydrolases. A structured family GH16 glycoside hydrolase database has been constructed (http://www. ghdb.uni-stuttgart.de) and provides multiple sequence alignments with functionally annotated amino acid residues and phylogenetic trees. The database has been used for homology modeling of seven glycoside hydrolases from the GH16 family with various substrate specificities, based on structural coordinates for (1,3;1,4)--D-glucan endohydrolases and a -carrageenase. In combination with multiple sequence alignments, the models predict the three-dimensional (3D) dispositions of amino acid residues in the substratebinding and catalytic sites of XTHs and (1,3/1,3;1,4)--D-glucan endohydrolases; there is no structural information available in the databases for the latter group of enzymes. Models of the XTHs, compared with the recently determined structure of a Populus tremulos × tremuloides XTH, reveal similarities with the active sites of family GH11 (1,4)--D-xylan endohydrolases. From a biological viewpoint, the classification, molecular modeling and a new 3D structure of the P. tremulos × tremuloides XTH establish structural and evolutionary connections between XTHs, (1,3;1,4)--D-glucan endohydrolases and xylan endohydrolases. These findings raise the possibility that XTHs from higher plants could be active not only on cell wall xyloglucans, but also on (1,3;1,4)--D-glucans and arabinoxylans, which are major components of walls in grasses. A role for XTHs in (1,3;1,4)--D-glucan and arabinoxylan modification would be consistent with the apparent overrepresentation of XTH sequences in cereal expressed sequence tags databases.
Bioinformatics and molecular modeling in chemical enzymology. Active sites of hydrolases
Biochemistry. Biokhimii͡a, 2002
Comparison and multiple alignments of amino acid sequences of a representative number of related enzymes demonstrate the existence of certain positions of amino acid residues which are permanently reproducible in all members of the whole family. The use of the bioinformatic approach revealed conservative residues in each of the related enzymes and ranked amino acid conservatism for the overall enzymatic catalysis. Glycine and aspartic acid residues were shown to be the most essential for structure and catalytic activity of enzymes. Amino acid residues forming catalytic subsite of the active site of enzymes are always highly conservative. Analysis revealed that aspartic acid carboxyl group is the most frequently employed nucleophilic (in deprotonated form) and electrophilic (in protonated form) agent involved in activation of molecules by the mechanism of general base and acidic catalyses in the catalytic sites of enzymes. Glycine is a unique amino acid possessing the highest possibi...