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1c3b
From Proteopedia
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|PDB= 1c3b |SIZE=350|CAPTION= <scene name='initialview01'>1c3b</scene>, resolution 2.25Å | |PDB= 1c3b |SIZE=350|CAPTION= <scene name='initialview01'>1c3b</scene>, resolution 2.25Å | ||
|SITE= | |SITE= | ||
| - | |LIGAND= <scene name='pdbligand=BZB:BENZO[B]THIOPHENE-2-BORONIC ACID'>BZB</scene> | + | |LIGAND= <scene name='pdbligand=BZB:BENZO[B]THIOPHENE-2-BORONIC+ACID'>BZB</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= | |GENE= | ||
| + | |DOMAIN= | ||
| + | |RELATEDENTRY=[[2bls|2BLS]], [[3bls|3BLS]] | ||
| + | |RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1c3b FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1c3b OCA], [http://www.ebi.ac.uk/pdbsum/1c3b PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1c3b RCSB]</span> | ||
}} | }} | ||
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[[Category: Shoichet, B K.]] | [[Category: Shoichet, B K.]] | ||
[[Category: Weston, G S.]] | [[Category: Weston, G S.]] | ||
| - | [[Category: BZB]] | ||
[[Category: beta-lactamase]] | [[Category: beta-lactamase]] | ||
[[Category: cephalosporinase]] | [[Category: cephalosporinase]] | ||
[[Category: serine hydrolase]] | [[Category: serine hydrolase]] | ||
| - | ''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 19:13:41 2008'' |
Revision as of 16:13, 30 March 2008
| |||||||
| , resolution 2.25Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | |||||||
| Activity: | Beta-lactamase, with EC number 3.5.2.6 | ||||||
| Related: | 2BLS, 3BLS
| ||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
AMPC BETA-LACTAMASE FROM E. COLI COMPLEXED WITH INHIBITOR, BENZO(B)THIOPHENE-2-BORONIC ACID (BZB)
Overview
Beta-lactamases are the major resistance mechanism to beta-lactam antibiotics and pose a growing threat to public health. Recently, bacteria have become resistant to beta-lactamase inhibitors, making this problem pressing. In an effort to overcome this resistance, non-beta-lactam inhibitors of beta-lactamases were investigated for complementarity to the structure of AmpC beta-lactamase from Escherichia coli. This led to the discovery of an inhibitor, benzo(b)thiophene-2-boronic acid (BZBTH2B), which inhibited AmpC with a Ki of 27 nM. This inhibitor is chemically dissimilar to beta-lactams, raising the question of what specific interactions are responsible for its activity. To answer this question, the X-ray crystallographic structure of BZBTH2B in complex with AmpC was determined to 2.25 A resolution. The structure reveals several unexpected interactions. The inhibitor appears to complement the conserved, R1-amide binding region of AmpC, despite lacking an amide group. Interactions between one of the boronic acid oxygen atoms, Tyr150, and an ordered water molecule suggest a mechanism for acid/base catalysis and a direction for hydrolytic attack in the enzyme catalyzed reaction. To investigate how a non-beta-lactam inhibitor would perform against resistant bacteria, BZBTH2B was tested in antimicrobial assays. BZBTH2B significantly potentiated the activity of a third-generation cephalosporin against AmpC-producing resistant bacteria. This inhibitor was unaffected by two common resistance mechanisms that often arise against beta-lactams in conjunction with beta-lactamases. Porin channel mutations did not decrease the efficacy of BZBTH2B against cells expressing AmpC. Also, this inhibitor did not induce expression of AmpC, a problem with many beta-lactams. The structure of the BZBTH2B/AmpC complex provides a starting point for the structure-based elaboration of this class of non-beta-lactam inhibitors.
About this Structure
1C3B is a Single protein structure of sequence from Escherichia coli. Full crystallographic information is available from OCA.
Reference
The complexed structure and antimicrobial activity of a non-beta-lactam inhibitor of AmpC beta-lactamase., Powers RA, Blazquez J, Weston GS, Morosini MI, Baquero F, Shoichet BK, Protein Sci. 1999 Nov;8(11):2330-7. PMID:10595535
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