title: Structural modelling of substrate binding and inhibition in penicillin V acylase from Pectobacterium atrosepticum.
abstract: Penicillin V acylases (PVAs) and bile salt hydrolases (BSHs) have considerable sequence and structural similarity; however, they vary significantly in their substrate specificity. We have identified a PVA from a Gram-negative organism, Pectobacterium atrosepticum (PaPVA) that turned out to be a remote homolog of the PVAs and BSHs reported earlier. Even though the active site residues were conserved in PaPVA it showed high specificity towards penV and interestingly the penV acylase activity was inhibited by bile salts. Comparative modelling and docking studies were carried out to understand the structural differences of the binding site that confer this characteristic property. We show that PaPVA exhibits significant differences in structure, which are in contrast to those of known PVAs and such enzymes from Gram-negative bacteria require further investigation.
authors.affiliation: Division of Biochemical Sciences, National Chemical Laboratory, Pune, India.
authors.forename: V S
authors.initials: VS
authors.lastname: Avinash
authors.forename: Priyabrata
authors.initials: P
authors.lastname: Panigrahi
authors.forename: C G
authors.initials: CG
authors.lastname: Suresh
authors.forename: Archana V
authors.initials: AV
authors.lastname: Pundle
authors.forename: Sureshkumar
authors.initials: S
authors.lastname: Ramasamy
mesh_terms: D000581:Amidohydrolases / Q000737:chemistry; D001426:Bacterial Proteins / Q000737:chemistry*; D001647:Bile Acids and Salts / Q000737:chemistry; D020134:Catalytic Domain; D004305:Dose-Response Relationship, Drug; D006860:Hydrogen Bonding; D006868:Hydrolysis; D062105:Molecular Docking Simulation; D044043:Pectobacterium / Q000201:enzymology*; D010399:Penicillin Amidase / Q000737:chemistry*; D011485:Protein Binding; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D013379:Substrate Specificity
chemical_list: D001426:Bacterial Proteins; D001647:Bile Acids and Salts; D000581:Amidohydrolases; D010399:Penicillin Amidase; C023154:choloylglycine hydrolase
keywords: Bile salt hydrolase; Docking; Homology modelling; Inhibition; Pectobacterium; Penicillin acylase