7l5f

Crystal Structure of N-(2-oxocyclobutyl) decanamide Bound AiiA-Co

spinqualitylabelsall models 7l5f, resolution 1.51Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 7l5f is a 1 chain structure with sequence from Bacillus subtilis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.51Å Ligands: CO, GOL, XNG Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function AHLLA_BACTK Catalyzes hydrolysis of N-hexanoyl-(S)-homoserine lactone, but not the R-enantiomer. Hydrolyzes short- and long-chain N-acyl homoserine lactones with or without 3-oxo substitution at C3, has maximum activity on C10-AHL. Publication Abstract from PubMed An alpha-amido cyclobutanone possessing a C10 hydrocarbon tail was designed as a potential transition-state mimetic for the quorum-quenching metallo-gamma-lactonase autoinducer inactivator A (AiiA) with the support of in-house modeling techniques and found to be a competitive inhibitor of dicobalt(II) AiiA with an inhibition constant of K i = 0.007 +/- 0.002 mM. The catalytic mechanism of AiiA was further explored using our product-based transition-state modeling (PBTSM) computational approach, providing substrate-intermediate models arising during enzyme turnover and further insight into substrate-enzyme interactions governing native substrate catalysis. These interactions were targeted in the docking of cyclobutanone hydrates into the active site of AiiA. The X-ray crystal structure of dicobalt(II) AiiA cocrystallized with this cyclobutanone inhibitor unexpectedly revealed an N-(2-oxocyclobutyl)decanamide ring-opened acyclic product bound to the enzyme active site (PDB 7L5F). The C10 alkyl chain and its interaction with the hydrophobic phenylalanine clamp region of AiiA adjacent to the active site enabled atomic placement of the ligand atoms, including the C10 alkyl chain. A mechanistic hypothesis for the ring opening is proposed involving a radical-mediated process. Cyclobutanone Inhibitor of Cobalt-Functionalized Metallo-gamma-Lactonase AiiA with Cyclobutanone Ring Opening in the Active Site.,Reidl CT, Mascarenhas R, Mohammad TSH, Lutz MR Jr, Thomas PW, Fast W, Liu D, Becker DP ACS Omega. 2021 May 17;6(21):13567-13578. doi: 10.1021/acsomega.0c06348., eCollection 2021 Jun 1. PMID:34095651 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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