1a8t

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[[Image:1a8t.gif|left|200px]]<br /><applet load="1a8t" size="350" color="white" frame="true" align="right" spinBox="true"
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[[Image:1a8t.gif|left|200px]]
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caption="1a8t, resolution 2.55&Aring;" />
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'''METALLO-BETA-LACTAMASE IN COMPLEX WITH L-159,061'''<br />
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{{Structure
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|PDB= 1a8t |SIZE=350|CAPTION= <scene name='initialview01'>1a8t</scene>, resolution 2.55&Aring;
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|SITE=
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|LIGAND= <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene> and <scene name='pdbligand=061:2-BUTYL-6-HYDROXY-3-[2'-(1H-TETRAZOL-5-YL)-BIPHENYL-4-YLMETHYL]-3H-QUINAZOLIN-4-ONE'>061</scene>
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|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]
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|GENE= CCRA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=817 Bacteroides fragilis])
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}}
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'''METALLO-BETA-LACTAMASE IN COMPLEX WITH L-159,061'''
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==Overview==
==Overview==
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==About this Structure==
==About this Structure==
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1A8T is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Bacteroides_fragilis Bacteroides fragilis] with <scene name='pdbligand=ZN:'>ZN</scene> and <scene name='pdbligand=061:'>061</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A8T OCA].
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1A8T is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Bacteroides_fragilis Bacteroides fragilis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1A8T OCA].
==Reference==
==Reference==
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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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9545432 9545432]
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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:[http://www.ncbi.nlm.nih.gov/pubmed/9545432 9545432]
[[Category: Bacteroides fragilis]]
[[Category: Bacteroides fragilis]]
[[Category: Beta-lactamase]]
[[Category: Beta-lactamase]]
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[[Category: zinc]]
[[Category: zinc]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 11:42:13 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 09:54:33 2008''

Revision as of 07:54, 20 March 2008

Image:1a8t.gif


PDB ID 1a8t

Drag the structure with the mouse to rotate
, resolution 2.55Å
Ligands: and
Gene: CCRA (Bacteroides fragilis)
Activity: Beta-lactamase, with EC number 3.5.2.6
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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