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1pw8
From Proteopedia
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| - | [[Image:1pw8.jpg|left|200px]] | + | [[Image:1pw8.jpg|left|200px]] |
| - | + | ||
| - | '''Covalent Acyl Enzyme Complex Of The R61 DD-Peptidase with A Highly Specific Cephalosporin''' | + | {{Structure |
| + | |PDB= 1pw8 |SIZE=350|CAPTION= <scene name='initialview01'>1pw8</scene>, resolution 1.30Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=H2A:(6R,7R)-3-[(ACETYLOXY)METHYL]-7-{[(6S)-6-(GLYCYLAMINO)-7-OXIDO-7-OXOHEPTANOYL]AMINO}-8-OXO-5-THIA-1-AZABICYCLO[4.2.0]OCTANE-2-CARBOXYLATE'>H2A</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</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 Acyl Enzyme Complex Of The R61 DD-Peptidase with A Highly Specific Cephalosporin''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1PW8 is a [ | + | 1PW8 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=1PW8 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: GOL]] | [[Category: GOL]] | ||
[[Category: H2A]] | [[Category: H2A]] | ||
| - | [[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 13:29:46 2008'' |
Revision as of 11:29, 20 March 2008
| |||||||
| , resolution 1.30Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Activity: | Serine-type D-Ala-D-Ala carboxypeptidase, with EC number 3.4.16.4 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Covalent Acyl Enzyme Complex Of The R61 DD-Peptidase with A Highly Specific Cephalosporin
Overview
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 Structure
1PW8 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
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