1pw1
From Proteopedia
| Line 4: | Line 4: | ||
|PDB= 1pw1 |SIZE=350|CAPTION= <scene name='initialview01'>1pw1</scene>, resolution 1.20Å | |PDB= 1pw1 |SIZE=350|CAPTION= <scene name='initialview01'>1pw1</scene>, resolution 1.20Å | ||
|SITE= | |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> | + | |LIGAND= <scene name='pdbligand=FLH:FORMALDEHYDE'>FLH</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <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= <span class='plainlinks'>[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] </span> | |
|GENE= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[1mpl|1MPL]], [[1ikg|1IKG]], [[1iki|1IKI]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1pw1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pw1 OCA], [http://www.ebi.ac.uk/pdbsum/1pw1 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1pw1 RCSB]</span> | ||
}} | }} | ||
| Line 27: | Line 30: | ||
[[Category: Pratt, R F.]] | [[Category: Pratt, R F.]] | ||
[[Category: Silvaggi, N R.]] | [[Category: Silvaggi, N R.]] | ||
| - | [[Category: FLH]] | ||
| - | [[Category: GOL]] | ||
| - | [[Category: HEL]] | ||
[[Category: antibiotic]] | [[Category: antibiotic]] | ||
[[Category: beta-lactam]] | [[Category: beta-lactam]] | ||
| Line 36: | Line 36: | ||
[[Category: peptidoglycan]] | [[Category: peptidoglycan]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 23:05:18 2008'' |
Revision as of 20:05, 30 March 2008
| |||||||
| , resolution 1.20Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , , | ||||||
| Activity: | Serine-type D-Ala-D-Ala carboxypeptidase, with EC number 3.4.16.4 | ||||||
| Related: | 1MPL, 1IKG, 1IKI
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
Non-Covalent Complex Of Streptomyces R61 DD-Peptidase With A Highly Specific Penicillin
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
1PW1 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 Mar 30 23:05:18 2008
