1a8t
From Proteopedia
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|PDB= 1a8t |SIZE=350|CAPTION= <scene name='initialview01'>1a8t</scene>, resolution 2.55Å | |PDB= 1a8t |SIZE=350|CAPTION= <scene name='initialview01'>1a8t</scene>, resolution 2.55Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= | + | |LIGAND= <scene name='pdbligand=061:2-BUTYL-6-HYDROXY-3-[2'-(1H-TETRAZOL-5-YL)-BIPHENYL-4-YLMETHYL]-3H-QUINAZOLIN-4-ONE'>061</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> |
| - | |ACTIVITY= [http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] | + | |ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Beta-lactamase Beta-lactamase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.5.2.6 3.5.2.6] </span> |
|GENE= CCRA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=817 Bacteroides fragilis]) | |GENE= CCRA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=817 Bacteroides fragilis]) | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY= | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1a8t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1a8t OCA], [http://www.ebi.ac.uk/pdbsum/1a8t PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1a8t RCSB]</span> | ||
}} | }} | ||
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[[Category: Toney, J H.]] | [[Category: Toney, J H.]] | ||
[[Category: Vanderwall, D.]] | [[Category: Vanderwall, D.]] | ||
| - | [[Category: 061]] | ||
| - | [[Category: ZN]] | ||
[[Category: antibiotic resistance]] | [[Category: antibiotic resistance]] | ||
[[Category: beta-lactamase]] | [[Category: beta-lactamase]] | ||
| Line 35: | Line 36: | ||
[[Category: zinc]] | [[Category: zinc]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 18:35:42 2008'' |
Revision as of 15:35, 30 March 2008
| |||||||
| , resolution 2.55Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | , | ||||||
| Gene: | CCRA (Bacteroides fragilis) | ||||||
| Activity: | Beta-lactamase, with EC number 3.5.2.6 | ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
METALLO-BETA-LACTAMASE IN COMPLEX WITH L-159,061
Overview
BACKGROUND: High level resistance to carbapenem antibiotics in gram negative bacteria such as Bacteroides fragilis is caused, in part, by expression of a wide-spectrum metallo-beta-lactamase that hydrolyzes the drug to an inactive form. Co-administration of metallo-beta-lactamase inhibitors to resistant bacteria is expected to restore the antibacterial activity of carbapenems. RESULTS: Biphenyl tetrazoles (BPTs) are a structural class of potent competitive inhibitors of metallo-beta-lactamase identified through screening and predicted using molecular modeling of the enzyme structure. The X-ray crystal structure of the enzyme bound to the BPT L-159,061 shows that the tetrazole moiety of the inhibitor interacts directly with one of the two zinc atoms in the active site, replacing a metal-bound water molecule. Inhibition of metallo-beta-lactamase by BPTs in vitro correlates well with antibiotic sensitization of resistant B. fragilis. CONCLUSIONS: BPT inhibitors can sensitize a resistant B. fragilis clinical isolate expressing metallo-beta-lactamase to the antibiotics imipenem or penicillin G but not to rifampicin.
About this Structure
1A8T is a Single protein structure of sequence from Bacteroides fragilis. Full crystallographic information is available from OCA.
Reference
Antibiotic sensitization using biphenyl tetrazoles as potent inhibitors of Bacteroides fragilis metallo-beta-lactamase., Toney JH, Fitzgerald PM, Grover-Sharma N, Olson SH, May WJ, Sundelof JG, Vanderwall DE, Cleary KA, Grant SK, Wu JK, Kozarich JW, Pompliano DL, Hammond GG, Chem Biol. 1998 Apr;5(4):185-96. PMID:9545432
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