3eqv | pdb_00003eqv

Crystal structure of penicillin-binding protein 2 from Neisseria gonorrhoeae containing four mutations associated with penicillin resistance

spinqualitylabelsall models 3eqv, resolution 2.40Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3eqv is a 2 chain structure with sequence from "diplococcus_gonorrhoeae"_(zopf_1885)_lehmann_and_neumann_1896 "diplococcus gonorrhoeae" (zopf 1885) lehmann and neumann 1896. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: GOL, SO4 NonStd Res: SEP Related: 3equ Gene: penA ("Diplococcus gonorrhoeae" (Zopf 1885) Lehmann and Neumann 1896) Activity: Serine-type D-Ala-D-Ala carboxypeptidase, with EC number 3.4.16.4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function [PBP2_NEIGO] Synthesis of cross-linked peptidoglycan from the lipid intermediates. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Penicillin-binding protein 2 (PBP2) from N. gonorrhoeae is the major molecular target for beta-lactam antibiotics used to treat gonococcal infections. PBP2 from penicillin-resistant strains of N. gonorrhoeae harbors an aspartate insertion after position 345 (Asp-345a) and 4-8 additional mutations, but how these alter the architecture of the protein is unknown. We have determined the crystal structure of PBP2 derived from the penicillin-susceptible strain FA19, which shows that the likely effect of Asp-345a is to alter a hydrogen-bonding network involving Asp-346 and the SXN triad at the active site. We have also solved the crystal structure of PBP2 derived from the penicillin-resistant strain FA6140 that contains four mutations near the C terminus of the protein. Although these mutations lower the second order rate of acylation for penicillin by 5-fold relative to wild type, comparison of the two structures shows only minor structural differences, with the positions of the conserved residues in the active site essentially the same in both. Kinetic analyses indicate that two mutations, P551S and F504L, are mainly responsible for the decrease in acylation rate. Melting curves show that the four mutations lower the thermal stability of the enzyme. Overall, these data suggest that the molecular mechanism underlying antibiotic resistance contributed by the four mutations is subtle and involves a small but measurable disordering of residues in the active site region that either restricts the binding of antibiotic or impedes conformational changes that are required for acylation by beta-lactam antibiotics. Crystal structures of penicillin-binding protein 2 from penicillin-susceptible and -resistant strains of Neisseria gonorrhoeae reveal an unexpectedly subtle mechanism for antibiotic resistance.,Powell AJ, Tomberg J, Deacon AM, Nicholas RA, Davies C J Biol Chem. 2009 Jan 9;284(2):1202-12. Epub 2008 Nov 4. PMID:18986991 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Penicillin-binding protein 3D structures

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