View source for 8bv4


==Structure of BlaC from Mycobacterium tuberculosis in complex with vaborbactam==
<StructureSection load='8bv4' size='340' side='right'caption='[[8bv4]], [[Resolution|resolution]] 1.95&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8bv4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8BV4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8BV4 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.95&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4D6:{(3R,6S)-2-HYDROXY-3-[(THIOPHEN-2-YLACETYL)AMINO]-1,2-OXABORINAN-6-YL}ACETIC+ACID'>4D6</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8bv4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8bv4 OCA], [https://pdbe.org/8bv4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8bv4 RCSB], [https://www.ebi.ac.uk/pdbsum/8bv4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8bv4 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BLAC_MYCTA BLAC_MYCTA] Extended spectrum beta-lactamase (ESBL) that inactivates beta-lactam antibiotics by hydrolyzing the amide group of the beta-lactam ring. Exhibits predominant penicillinase activity. Also displays high levels of cephalosporinase activity as well as measurable activity with carbapenems, including imipenem and meropenem. Plays a primary role in the intrinsic resistance of M.tuberculosis to beta-lactam antibiotics.[UniProtKB:P9WKD3]<ref>PMID:9624479</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Conserved residues are often considered essential for function, and substitutions in such residues are expected to have a negative influence on the properties of a protein. However, mutations in a few highly conserved residues of the beta-lactamase from Mycobacterium tuberculosis, BlaC, were shown to have no or only limited negative effect on the enzyme. One such mutant, D179N, even conveyed increased ceftazidime resistance upon bacterial cells, while displaying good activity against penicillins. The crystal structures of BlaC D179N in resting state and in complex with sulbactam reveal subtle structural changes in the Omega-loop as compared to the structure of wild-type BlaC. Introducing this mutation in four other beta-lactamases, CTX-M-14, KPC-2, NMC-A and TEM-1, resulted in decreased antibiotic resistance for penicillins and meropenem. The results demonstrate that the Asp in position 179 is generally essential for class A beta-lactamases but not for BlaC, which can be explained by the importance of the interaction with the side chain of Arg164 that is absent in BlaC. It is concluded that Asp179 though conserved is not essential in BlaC, as a consequence of epistasis.

Asp179 in the class A beta-lactamase from Mycobacterium tuberculosis is a conserved yet not essential residue due to epistasis.,van Alen I, Chikunova A, van Zanten DB, de Block AA, Timmer M, Brunle S, Ubbink M FEBS J. 2023 Jun 19. doi: 10.1111/febs.16892. PMID:37335937<ref>PMID:37335937</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8bv4" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Bruenle S]]
[[Category: Chikunova A]]
[[Category: Ubbink M]]