1pwg

Covalent Penicilloyl Acyl Enzyme Complex Of The Streptomyces R61 DD-Peptidase With A Highly Specific PenicillinCovalent Penicilloyl Acyl Enzyme Complex Of The Streptomyces R61 DD-Peptidase With A Highly Specific Penicillin

Structural highlights 1pwg is a 1 chain structure with sequence from Streptomyces sp.. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: Related: 1mpl, 1ikg, 1iki Activity: Serine-type D-Ala-D-Ala carboxypeptidase, with EC number 3.4.16.4 Resources: FirstGlance, OCA, RCSB, PDBsum Function [DAC_STRSR] Catalyzes distinct carboxypeptidation and transpeptidation reactions during the last stages of wall peptidoglycan synthesis. Mistaking a beta-lactam antibiotic molecule for a normal substrate (i.e. a D-alanyl-D-alanine-terminated peptide), it becomes immobilized in the form of a long-lived, serine-ester-linked acyl enzyme and thus behave as penicillin-binding protein (PBP). 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 The bacterial D-alanyl-D-alanine transpeptidases (DD-peptidases) are the killing targets of beta-lactams, the most important clinical defense against bacterial infections. However, due to the constant development of antibiotic-resistance mechanisms by bacteria, there is an ever-present need for new, more effective antimicrobial drugs. While enormous numbers of beta-lactam compounds have been tested for antibiotic activity in over 50 years of research, the success of a beta-lactam structure in terms of antibiotic activity remains unpredictable. Tipper and Strominger suggested long ago that beta-lactams inhibit DD-peptidases because they mimic the D-alanyl-D-alanine motif of the peptidoglycan substrate of these enzymes. They also predicted that beta-lactams having a peptidoglycan-mimetic side-chain might be better antibiotics than their non-specific counterparts, but decades of research have not provided any evidence for this. We have recently described two such novel beta-lactams. The first is a penicillin having the glycyl-L-alpha-amino-epsilon-pimelyl side-chain of Streptomyces strain R61 peptidoglycan, making it the "perfect penicillin" for this organism. The other is a cephalosporin with the same side-chain. Here, we describe the X-ray crystal structures of the perfect penicillin in non-covalent and covalent complexes with the Streptomyces R61 DD-peptidase. The structure of the non-covalent enzyme-inhibitor complex is the first such complex to be trapped crystallographically with a DD-peptidase. In addition, the covalent complex of the peptidyl-cephalosporin with the R61 DD-peptidase is described. Finally, two covalent complexes with the traditional beta-lactams benzylpenicillin and cephalosporin C were determined for comparison with the peptidyl beta-lactams. These structures, together with relevant kinetics data, support Tipper and Strominger's assertion that peptidoglycan-mimetic side-chains should improve beta-lactams as inhibitors of DD-peptidases. Crystal structures of complexes between the R61 DD-peptidase and peptidoglycan-mimetic beta-lactams: a non-covalent complex with a "perfect penicillin".,Silvaggi NR, Josephine HR, Kuzin AP, Nagarajan R, Pratt RF, Kelly JA J Mol Biol. 2005 Jan 21;345(3):521-33. PMID:15581896 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Penicillin-binding protein

spinqualitylabelsall models 1pwg, resolution 1.07Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image