PMID:17362992
| Citation |
Agarwal, R, Burley, SK and Swaminathan, S (2007) Structural analysis of a ternary complex of allantoate amidohydrolase from Escherichia coli reveals its mechanics. J. Mol. Biol. 368:450-63 |
|---|---|
| Abstract |
Purine metabolism plays a major role in regulating the availability of purine nucleotides destined for nucleic acid synthesis. Allantoate amidohydrolase catalyzes the conversion of allantoate to (S)-ureidoglycolate, one of the crucial alternate steps in purine metabolism. The crystal structure of a ternary complex of allantoate amidohydrolase with its substrate allantoate and an allosteric effector, a sulfate ion, from Escherichia coli was determined to understand better the catalytic mechanism and substrate specificity. The 2.25 A resolution X-ray structure reveals an alpha/beta scaffold akin to zinc exopeptidases of the peptidase M20 family and lacks the (beta/alpha)(8)-barrel fold characteristic of the amidohydrolases. Arrangement of the substrate and the two co-catalytic zinc ions at the active site governs catalytic specificity for hydrolysis of N-carbamyl versus the peptide bond in exopeptidases. In its crystalline form, allantoate amidohydrolase adopts a relatively open conformation. However, structural analysis reveals the possibility of a significant movement of domains via rotation about two hinge regions upon allosteric effector and substrate binding resulting in a closed catalytically competent conformation by bringing the substrate allantoate closer to co-catalytic zinc ions. Two cis-prolyl peptide bonds found on either side of the dimerization domain in close proximity to the substrate and ligand-binding sites may be involved in protein folding and in preserving the integrity of the catalytic site. |
| Links |
PubMed Online version:10.1016/j.jmb.2007.02.028 |
| Keywords |
Allantoin/chemistry; Allantoin/metabolism; Allosteric Site; Amino Acid Sequence; Binding Sites; Catalysis; Catalytic Domain; Crystallography, X-Ray; Dimerization; Enzyme Stability; Escherichia coli/enzymology; Evolution, Molecular; Exopeptidases/metabolism; Ligands; Molecular Sequence Data; Peptides/chemistry; Protein Folding; Protein Structure, Tertiary; Structural Homology, Protein; Structure-Activity Relationship; Substrate Specificity; Ureohydrolases/chemistry; Ureohydrolases/metabolism; Zinc/metabolism |
| edit table |
Significance
You can help EcoliWiki by summarizing why this paper is useful
Useful Materials and Methods
You can help Ecoliwiki by describing the useful materials (strains, plasmids, antibodies, etc) described in this paper.
Annotations
<protect><annotationlinks/></protect>
EcoliWiki Links
Add links to pages that link here (e.g. gene, product, method pages)
See also
References
See Help:References for how to manage references in EcoliWiki.
