View source for 8rg2


==Structure of BlaC from Mycobacterium tuberculosis at pH 8==
<StructureSection load='8rg2' size='340' side='right'caption='[[8rg2]], [[Resolution|resolution]] 1.80&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8rg2]] 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=8RG2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8RG2 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]] 1.8&#8491;</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=8rg2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8rg2 OCA], [https://pdbe.org/8rg2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8rg2 RCSB], [https://www.ebi.ac.uk/pdbsum/8rg2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8rg2 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BLAC_MYCTU BLAC_MYCTU] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Serine beta-lactamases inactivate beta-lactam antibiotics in a two-step mechanism comprising acylation and deacylation. For the deacylation step, a water molecule is activated by a conserved glutamate residue to release the adduct from the enzyme. The third-generation cephalosporin ceftazidime is a poor substrate for the class A beta-lactamase BlaC from Mycobacterium tuberculosis but it can be hydrolyzed faster when the active site pocket is enlarged, as was reported for mutant BlaC P167S. The conformational change in the Omega-loop of the P167S mutant displaces the conserved glutamate (Glu166), suggesting it is not required for deacylation of the ceftazidime adduct. Here, we report the characterization of wild type BlaC and BlaC E166A at various pH values. The presence of Glu166 strongly enhances activity against nitrocefin but not ceftazidime, indicating it is indeed not required for deacylation of the adduct of the latter substrate. At high pH wild type BlaC was found to exist in two states, one of which converts ceftazidime much faster, resembling the open state previously reported for the BlaC mutant P167S. The pH-dependent switch between the closed and open states is caused by the loss at high pH of a low-barrier hydrogen bond, a proton shared between Asp172 and Asp179. These results illustrate how readily shifts in substrate specificity can occur as a consequence of subtle changes in protein structure.

A low-barrier proton shared between two aspartates acts as a conformational switch that changes the substrate specificity of the beta-lactamase BlaC.,Sun J, Boyle AL, Brunle S, Ubbink M Int J Biol Macromol. 2024 Aug 10;278(Pt 2):134665. doi: , 10.1016/j.ijbiomac.2024.134665. PMID:39134195<ref>PMID:39134195</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8rg2" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Bruenle S]]
[[Category: Sun J]]
[[Category: Ubbink M]]