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| | {{STRUCTURE_1pwg| PDB=1pwg | SCENE= }} | | {{STRUCTURE_1pwg| PDB=1pwg | SCENE= }} |
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| - | '''Covalent Penicilloyl Acyl Enzyme Complex Of The Streptomyces R61 DD-Peptidase With A Highly Specific Penicillin'''
| + | ===Covalent Penicilloyl Acyl Enzyme Complex Of The Streptomyces R61 DD-Peptidase With A Highly Specific Penicillin=== |
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| - | ==Overview==
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| - | 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. | + | The line below this paragraph, {{ABSTRACT_PUBMED_15581896}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 15581896 is the PubMed ID number. |
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| | + | {{ABSTRACT_PUBMED_15581896}} |
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| | ==About this Structure== | | ==About this Structure== |
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| | [[Category: Penicillin binding protein]] | | [[Category: Penicillin binding protein]] |
| | [[Category: Peptidoglycan]] | | [[Category: Peptidoglycan]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 05:34:04 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 18:11:41 2008'' |
Revision as of 15:11, 27 July 2008
Template:STRUCTURE 1pwg
Covalent Penicilloyl Acyl Enzyme Complex Of The Streptomyces R61 DD-Peptidase With A Highly Specific Penicillin
Template:ABSTRACT PUBMED 15581896
About this Structure
1PWG is a Single protein structure of sequence from Streptomyces sp.. Full crystallographic information is available from OCA.
Reference
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
Page seeded by OCA on Sun Jul 27 18:11:41 2008
