3mze | pdb_00003mze

Structure of penicillin-binding protein 5 from E.coli: cefoxitin acyl-enzyme complex

spinqualitylabelsall models 3mze, resolution 2.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 3mze is a 1 chain structure with sequence from Escherichia coli K-12. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.1Å Ligands: 1QL, GOL Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function DACA_ECOLI Removes C-terminal D-alanyl residues from sugar-peptide cell wall precursors. Publication Abstract from PubMed Penicillin-binding proteins (PBPs) are the molecular targets for the widely used beta-lactam class of antibiotics, but how these compounds act at the molecular level is not fully understood. We have determined crystal structures of Escherichia coli PBP 5 as covalent complexes with imipenem, cloxacillin, and cefoxitin. These antibiotics exhibit very different second-order rates of acylation for the enzyme. In all three structures, there is excellent electron density for the central portion of the beta-lactam, but weak or absent density for the R1 or R2 side chains. Areas of contact between the antibiotics and PBP 5 do not correlate with the rates of acylation. The same is true for conformational changes, because although a shift of a loop leading to an electrostatic interaction between Arg248 and the beta-lactam carboxylate, which occurs completely with cefoxitin and partially with imipenem and is absent with cloxacillin, is consistent with the different rates of acylation, mutagenesis of Arg248 decreased the level of cefoxitin acylation only 2-fold. Together, these data suggest that structures of postcovalent complexes of PBP 5 are unlikely to be useful vehicles for the design of new covalent inhibitors of PBPs. Finally, superimposition of the imipenem-acylated complex with PBP 5 in complex with a boronic acid peptidomimetic shows that the position corresponding to the hydrolytic water molecule is occluded by the ring nitrogen of the beta-lactam. Because the ring nitrogen occupies a similar position in all three complexes, this supports the hypothesis that deacylation is blocked by the continued presence of the leaving group after opening of the beta-lactam ring. Crystal structures of covalent complexes of beta-lactam antibiotics with Escherichia coli penicillin-binding protein 5: toward an understanding of antibiotic specificity.,Nicola G, Tomberg J, Pratt RF, Nicholas RA, Davies C Biochemistry. 2010 Sep 21;49(37):8094-104. PMID:20726582 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Penicillin-binding protein 3D structures

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