1c3b

<StructureSection load='1c3b' size='340' side='right' caption='[[1c3b]], [[Resolution|resolution]] 2.25&Aring;' scene=''>

<table><tr><td colspan='2'>[[1c3b]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ecoli Ecoli]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1C3B OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1C3B FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BZB:BENZO[B]THIOPHENE-2-BORONIC+ACID'>BZB</scene></td></tr>

<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2bls|2bls]], [[3bls|3bls]]</td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><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></td></tr>

<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><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://pdbe.org/1c3b PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1c3b RCSB], [http://www.ebi.ac.uk/pdbsum/1c3b PDBsum]</span></td></tr>

[[http://www.uniprot.org/uniprot/AMPC_ECOLI AMPC_ECOLI]] This protein is a serine beta-lactamase with a substrate specificity for cephalosporins.

<scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/c3/1c3b_consurf.spt"</scriptWhenChecked>

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== Publication Abstract from PubMed ==

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.

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<ref>PMID:10595535</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 1c3b" style="background-color:#fffaf0;"></div>

== References ==

<references/>

[[Category: Beta-lactamase]]

[[Category: Ecoli]]

[[Category: Baquero, F]]

[[Category: Blazquez, J]]

[[Category: Morosini, M I]]

[[Category: Powers, R A]]

[[Category: Shoichet, B K]]

[[Category: Weston, G S]]

[[Category: Serine hydrolase]]