4ax1 | pdb_00004ax1

Q157N mutant. Crystal Structure of the Mobile Metallo-beta-Lactamase AIM-1 from Pseudomonas aeruginosa: Insights into Antibiotic Binding and the role of Gln157

spinqualitylabelsall models 4ax1, resolution 1.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4ax1 is a 1 chain structure with sequence from Pseudomonas aeruginosa. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 1.4Å Ligands: ACT, CA, MG, ZN Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function B5DCA0_PSEAI Publication Abstract from PubMed Metallo-beta-lactamase (MBL) genes confer resistance to virtually all beta-lactam antibiotics and are rapidly disseminated by mobile genetic elements in Gram-negative bacteria. MBLs belong to three different subgroups; B1, B2, and B3; with the mobile MBLs largely confined to subgroup B1. The B3 MBLs are a divergent subgroup of predominantly chromosomally encoded enzymes. AIM-1 (Adelaide IMipenmase) from Pseudomonas aeruginosa was the first B3 MBL to be identified on a readily mobile genetic element. Here we present the crystal structure of AIM-1, and use in silico docking and quantum and molecular mechanics (QM/MM) calculations, together with site-directed mutagenesis, to investigate its interaction with beta-lactams. AIM-1 adopts the characteristic alphabeta/betaalpha sandwich fold of MBLs, but differs from other B3 enzymes in the conformation of an active site loop (residues 156-162) which is involved both in disulfide bond formation and, we suggest, interaction with substrates. The structure, together with docking and QM/MM calculations, indicates that the AIM-1 substrate binding site is narrower and more restricted than those of other B3 MBLs, possibly explaining its higher catalytic efficiency. The location of Gln157 adjacent to the AIM-1 zinc center suggests a role in drug binding that is supported by our in silico studies, However, replacement of this residue by either Asn or Ala resulted in only modest reductions in AIM-1 activity against the majority of beta-lactam substrates, indicating that this function is non-essential. Our study reveals AIM-1 to be a subclass B3 MBL with novel structural and mechanistic features. Crystal Structure of the Mobile Metallo-beta-Lactamase AIM-1 from Pseudomonas aeruginosa: Insights into Antibiotic Binding and the role of Gln157.,Leiros HK, Borra PS, Brandsdal BO, Edvardsen KS, Spencer J, Walsh TR, Samuelsen O Antimicrob Agents Chemother. 2012 Jun 4. PMID:22664968 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta-lactamase 3D structures

Proteopedia Page Contributors and Editors (what is this?)

OCA