Structural Analysis of a Ternary Complex of Allantoate Amidohydrolase from Escherichia Coli Reveals Its Mechanics.
From: Biology Department, Brookhaven National Laboratory, Upton, NY 11973, USA.
Journal of molecular biology
- Publish Date: Apr 2007
- ISSN: 0022-2836
- Volume: 368
- Issue: 2
- Pages: 450-63
- Medium: Print
- Language: English
- Citation (JAMA): Agarwal Rakhi, Burley Stephen K, Swaminathan Subramanyam, et al. Structural Analysis of a Ternary Complex of Allantoate Amidohydrolase from Escherichia Coli Reveals Its Mechanics.. J. Mol. Biol. Apr 2007;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.
Mesh Headings (Keywords): Allantoin, Allosteric Site, Amino Acid Sequence, Binding Sites, Catalysis, Catalytic Domain, Crystallography, X-Ray, Dimerization, Enzyme Stability, Escherichia coli, Evolution, Molecular, Exopeptidases, Ligands, Molecular Sequence Data, Peptides, Protein Folding, Protein Structure, Tertiary, Structural Homology, Protein, Structure-Activity Relationship, Substrate Specificity, Ureohydrolases, Zinc
Check for Full Text / PubMed Unique Identifier (PMID): 17362992
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