View source for 3zhh


==X-ray structure of the full-length beta-lactamase from M.tuberculosis==
<StructureSection load='3zhh' size='340' side='right'caption='[[3zhh]], [[Resolution|resolution]] 2.85&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[3zhh]] is a 4 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=3ZHH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3ZHH 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]] 2.85&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=3zhh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zhh OCA], [https://pdbe.org/3zhh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3zhh RCSB], [https://www.ebi.ac.uk/pdbsum/3zhh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3zhh ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/BLAC_MYCTU BLAC_MYCTU] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Directed evolution can be a powerful tool for revealing the mutational pathways that lead to more resistant bacterial strains. In this study, we focused on the bacterium Mycobacterium tuberculosis, which is resistant to members of the beta-lactam class of antibiotics and thus continues to pose a major public health threat. Resistance of this organism is the result of a chromosomally encoded, extended spectrum class A beta-lactamase, BlaC, that is constitutively produced. Here, combinatorial enzyme libraries were selected on ampicillin to identify mutations that increased resistance of bacteria to beta-lactams. After just a single round of mutagenesis and selection, BlaC mutants were evolved that conferred 5-fold greater antibiotic resistance to cells and enhanced the catalytic efficiency of BlaC by 3-fold compared to the wild-type enzyme. All isolated mutants carried a mutation at position 105 (e.g., I105F) that appears to widen access to the active site by 3.6 A while also stabilizing the reorganized topology. In light of these findings, we propose that I105 is a 'gatekeeper' residue of the active site that regulates substrate hydrolysis by BlaC. Moreover, our results suggest that directed evolution can provide insight into the development of highly drug resistant microorganisms.

Directed Evolution of Mycobacterium tuberculosis beta-Lactamase Reveals Gatekeeper Residue That Regulates Antibiotic Resistance and Catalytic Efficiency.,Feiler C, Fisher AC, Boock JT, Marrichi MJ, Wright L, Schmidpeter PA, Blankenfeldt W, Pavelka M, Delisa MP PLoS One. 2013 Sep 4;8(9):e73123. doi: 10.1371/journal.pone.0073123. PMID:24023821<ref>PMID:24023821</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3zhh" style="background-color:#fffaf0;"></div>

==See Also==
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Blankenfeldt W]]
[[Category: DeLisa MP]]
[[Category: Feiler C]]
[[Category: Fisher AC]]
[[Category: Marrichi MJ]]
[[Category: Pavelka M]]
[[Category: Schmidpeter PAM]]
[[Category: Wright L]]