The Geometry of Interactions Between Catalytic Residues and Their Substrates.
From: EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SD, UK. torrance@ebi.ac.uk
Journal of molecular biology
- Publish Date: Jun 2007
- ISSN: 0022-2836
- Volume: 369
- Issue: 4
- Pages: 1140-52
- Medium: Print
- Language: English
- Citation (JAMA): Torrance James W, Holliday Gemma L, Mitchell John B O, et al. The Geometry of Interactions Between Catalytic Residues and Their Substrates.. J. Mol. Biol. Jun 2007;369:1140-52
Abstract
The process of deducing the catalytic mechanism of an enzyme from its structure is highly complex and requires extensive experimental work to validate a proposed mechanism. As one step towards improving the reliability of this process, we have gathered statistics describing the typical geometry of catalytic residues with regard to the substrate and one another. In order to analyse residue-substrate interactions, we have assembled a dataset of structures of enzymes of known mechanism bound to substrate, product, or a substrate analogue. Despite the challenges presented in obtaining such experimental data, we were able to include 42 enzyme structures. We have also assembled a separate dataset of catalytic residues which act upon other catalytic residues, using a set of 60 enzyme structures. For both datasets, we have extracted the distances between residues with a given catalytic function and their target moieties. The geometry of residues whose function involves the transfer or sharing of hydrogens (either with substrate or another residue) was analysed more closely. The results showed that the geometry for such productive interactions (prior to the transition state) closely resembles that seen in non-catalytic hydrogen bonds, with distances and angles in the normal expected range. Such statistics provide limits on “expected geometries” for catalytic residues, which will help to identify these residues and elucidate enzyme mechanisms.
Mesh Headings (Keywords): Binding Sites, Catalysis, Databases, Protein, Enzymes, Hydrogen Bonding, Molecular Structure, Protein Conformation, Substrate Specificity
Check for Full Text / PubMed Unique Identifier (PMID): 17466330
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