Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.1.4 (deaminase)
 5,113 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Molecular modelling was used to investigate the catalytic site of penicillin G acylase (PGA) by building up a simple enzyme-ligand model able to describe and predict the enzyme selectivity. The investigation was based on a double computational approach: first, the GRID computational procedure was applied to gain a qualitative description of the chemical features of the PGA active site; second, a classical "transition state approach" was used to simulate the tetrahedral intermediates and to evaluate their energies. GRID calculations employed different probes which gave a complete description of the chemical interactions occurring upon binding of different ligands, thus indicating those structures having good affinity with the active site of the enzyme. Tetrahedral intermediates were constructed on the basis of GRID results and provided both geometrical features and energies of enzyme-substrate interaction. Such energies were compared to experimental kinetic data obtained in the enzymatic acylation of L-phenylglycine methyl ester using various methyl phenylacetate derivatives. The good agreement of computational results with experimental evidence demonstrates the validity of the model as a rapid and flexible tool to describe and predict the enzyme selectivity.
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PMID:GRID/tetrahedral intermediate computational approach to the study of selectivity of penicillin G acylase in amide bond synthesis. 1242 6

A new bioinformatic methodology was developed founded on the Unsupervised Pattern Cognition Analysis of GRID-based BioGPS descriptors (Global Positioning System in Biological Space). The procedure relies entirely on three-dimensional structure analysis of enzymes and does not stem from sequence or structure alignment. The BioGPS descriptors account for chemical, geometrical and physical-chemical features of enzymes and are able to describe comprehensively the active site of enzymes in terms of "pre-organized environment" able to stabilize the transition state of a given reaction. The efficiency of this new bioinformatic strategy was demonstrated by the consistent clustering of four different Ser hydrolases classes, which are characterized by the same active site organization but able to catalyze different reactions. The method was validated by considering, as a case study, the engineering of amidase activity into the scaffold of a lipase. The BioGPS tool predicted correctly the properties of lipase variants, as demonstrated by the projection of mutants inside the BioGPS "roadmap".
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PMID:BioGPS descriptors for rational engineering of enzyme promiscuity and structure based bioinformatic analysis. 2535 70