4wl2

Structure of penicillin V acylase from Pectobacterium atrosepticum

spinqualitylabelsall models 4wl2, resolution 2.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4wl2 is a 8 chain structure with sequence from Pectobacterium atrosepticum SCRI1043. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.5Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function PAC_PECAS Catalyzes the hydrolysis of penicillin V to 6-aminopenicillanate (6-APA) (PubMed:23850621, PubMed:25931393, PubMed:26707624). Shows high specificity towards penicillin V (PubMed:23850621). Can use other beta-lactam substrates, including penicillin G, ampicillin, cephalexin, cloxacillin and dicloxacillin, but at a rate less than 10% of that of penicillin V (PubMed:23850621). Does not show any activity with glyco- or tauro-conjugated bile salts (PubMed:23850621). Publication Abstract from PubMed Penicillin V acylases (PVA) catalyze the deacylation of the beta-lactam antibiotic phenoxymethylpenicillin (Pen V). They are members of the Ntn hydrolase family and possess an N-terminal cysteine as the main catalytic nucleophile residue. They form the evolutionarily related cholylglycine hydrolase (CGH) group which includes bile salt hydrolases (BSH) responsible for bile deconjugation. Even though a few PVA and BSH structures have been reported, no structure of a functional PVA from Gram-negative bacteria is available. Here, we report the crystal structure of a highly active PVA from Gram-negative Pectobacterium atrosepticum (PaPVA) at 2.5A resolution. Structural comparison with PVAs from Gram-positive bacteria revealed that PaPVA had a distinctive tetrameric structure and active site organization. In addition, mutagenesis of key active site residues and biochemical characterization of the resultant variants elucidated the role of these residues in substrate binding and catalysis. The importance of residue Trp23 and Trp87 side chains in binding and correct positioning of Pen V by PVAs was confirmed using mutagenesis and substrate docking with a 15ns molecular dynamics simulation. These results establish the unique nature of Gram-negative CGHs and necessitate further research about their substrate spectrum. Structural analysis of a penicillin V acylase from Pectobacterium atrosepticum confirms the importance of two Trp residues for activity and specificity.,Avinash VS, Panigrahi P, Chand D, Pundle A, Suresh CG, Ramasamy S J Struct Biol. 2016 Feb;193(2):85-94. doi: 10.1016/j.jsb.2015.12.008. Epub 2015, Dec 18. PMID:26707624 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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