1pwg: Difference between revisions
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'''Covalent Penicilloyl Acyl Enzyme Complex Of The Streptomyces R61 DD-Peptidase With A Highly Specific Penicillin''' | {{Structure | ||
|PDB= 1pwg |SIZE=350|CAPTION= <scene name='initialview01'>1pwg</scene>, resolution 1.074Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=HEL:(2S,5R,6R)-6-{[(6R)-6-(GLYCYLAMINO)-7-OXIDO-7-OXOHEPTANOYL]AMINO}-3,3-DIMETHYL-7-OXO-4-THIA-1-AZABICYCLO[3.2.0]HEPTANE-2-CARBOXYLATE'>HEL</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Serine-type_D-Ala-D-Ala_carboxypeptidase Serine-type D-Ala-D-Ala carboxypeptidase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.16.4 3.4.16.4] | |||
|GENE= | |||
}} | |||
'''Covalent Penicilloyl Acyl Enzyme Complex Of The Streptomyces R61 DD-Peptidase With A Highly Specific Penicillin''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
1PWG is a [ | 1PWG is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Streptomyces_sp. Streptomyces sp.]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1PWG OCA]. | ||
==Reference== | ==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:[http:// | 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:[http://www.ncbi.nlm.nih.gov/pubmed/15581896 15581896] | ||
[[Category: Serine-type D-Ala-D-Ala carboxypeptidase]] | [[Category: Serine-type D-Ala-D-Ala carboxypeptidase]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: Silvaggi, N R.]] | [[Category: Silvaggi, N R.]] | ||
[[Category: HEL]] | [[Category: HEL]] | ||
[[Category: | [[Category: antibiotic]] | ||
[[Category: beta-lactam]] | [[Category: beta-lactam]] | ||
[[Category: enzyme]] | [[Category: enzyme]] | ||
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[[Category: peptidoglycan]] | [[Category: peptidoglycan]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:29:50 2008'' | ||
Revision as of 14:29, 20 March 2008
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| , resolution 1.074Å | |||||||
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| Ligands: | |||||||
| Activity: | Serine-type D-Ala-D-Ala carboxypeptidase, with EC number 3.4.16.4 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Covalent Penicilloyl Acyl Enzyme Complex Of The Streptomyces R61 DD-Peptidase With A Highly Specific Penicillin
OverviewOverview
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.
About this StructureAbout this Structure
1PWG is a Single protein structure of sequence from Streptomyces sp.. Full crystallographic information is available from OCA.
ReferenceReference
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
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