View source for 6h27


==Structure of S70C BlaC from Mycobacterium tuberculosis==
<StructureSection load='6h27' size='340' side='right' caption='[[6h27]], [[Resolution|resolution]] 1.63&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6h27]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/"bacillus_tuberculosis"_(zopf_1883)_klein_1884 "bacillus tuberculosis" (zopf 1883) klein 1884]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6H27 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6H27 FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=PG0:2-(2-METHOXYETHOXY)ETHANOL'>PG0</scene></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=6h27 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6h27 OCA], [http://pdbe.org/6h27 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6h27 RCSB], [http://www.ebi.ac.uk/pdbsum/6h27 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6h27 ProSAT]</span></td></tr>
</table>
== Function ==
[[http://www.uniprot.org/uniprot/BLAC_MYCBO BLAC_MYCBO]] Extended spectrum beta-lactamase (ESBL) that inactivates beta-lactam antibiotics by hydrolyzing the amide group of the beta-lactam ring. Displays high levels of penicillinase and cephalosporinase activity as well as measurable activity with carbapenems, including imipenem and meropenem. Plays a primary role in the intrinsic resistance of mycobacteria to beta-lactam antibiotics.[UniProtKB:P9WKD3] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Mycobacterium tuberculosis (Mtb), the main causative agent of tuberculosis (TB), is naturally resistant to beta-lactam antibiotics due to the production of the extended spectrum beta-lactamase BlaC. beta-Lactam/beta-lactamase inhibitor combination therapies can circumvent the BlaC-mediated resistance of Mtb and are promising treatment options against TB. However, still little is known of the exact mechanism of BlaC inhibition by the beta-lactamase inhibitors currently approved for clinical use, clavulanic acid, sulbactam, tazobactam, and avibactam. Here, we present the X-ray diffraction crystal structures of the acyl-enzyme adducts of wild-type BlaC with the four inhibitors. The +70 Da adduct derived from clavulanate and the trans-enamine acylation adducts of sulbactam and tazobactam are reported. BlaC in complex with avibactam revealed two inhibitor conformations. Preacylation binding could not be observed because inhibitor binding was not detected in BlaC variants carrying a substitution of the active site serine 70 to either alanine or cysteine, by crystallography, ITC or NMR. These results suggest that the catalytic serine 70 is necessary not only for enzyme acylation but also for increasing BlaC affinity for inhibitors in the preacylation state. The structure of BlaC with the serine to cysteine mutation showed a covalent linkage of the cysteine 70 Sgamma atom to the nearby amino group of lysine 73. The differences of adduct conformations between BlaC and other beta-lactamases are discussed.

New Conformations of Acylation Adducts of Inhibitors of beta-Lactamase from Mycobacterium tuberculosis.,Tassoni R, Blok A, Pannu NS, Ubbink M Biochemistry. 2019 Feb 19;58(7):997-1009. doi: 10.1021/acs.biochem.8b01085. Epub , 2019 Jan 30. PMID:30632739<ref>PMID:30632739</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6h27" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Pannu, N S]]
[[Category: Tassoni, R]]
[[Category: Ubbink, M]]
[[Category: Hydrolase]]