The Geometry of Interactions between Catalytic Residues and their Substrates

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 c...

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Bibliographic Details
Published in:Journal of molecular biology 2007-06, Vol.369 (4), p.1140-1152
Main Authors: Torrance, James W., Holliday, Gemma L., Mitchell, John B.O., Thornton, Janet M.
Format: Article
Language:English
Subjects:
Binding Sites
Catalysis
catalytic residue
catalytic site atlas
Databases, Protein
enzyme
Enzymes - chemistry
Enzymes - genetics
Hydrogen Bonding
MACiE
mechanism
Molecular Structure
Protein Conformation
Substrate Specificity
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Summary: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.
ISSN:0022-2836
1089-8638
DOI:10.1016/j.jmb.2007.03.055