2gdn: Difference between revisions
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< | ==Crystal structure of the Mycobacterium tuberculosis beta-lactamase== | ||
<StructureSection load='2gdn' size='340' side='right'caption='[[2gdn]], [[Resolution|resolution]] 1.72Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[2gdn]] 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=2GDN OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2GDN 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]] 1.72Å</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=2gdn FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gdn OCA], [https://pdbe.org/2gdn PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2gdn RCSB], [https://www.ebi.ac.uk/pdbsum/2gdn PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2gdn ProSAT], [https://www.topsan.org/Proteins/TBSGC/2gdn TOPSAN]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/BLAC_MYCTU BLAC_MYCTU] | |||
== Evolutionary Conservation == | |||
[[Image:Consurf_key_small.gif|200px|right]] | |||
Check<jmol> | |||
<jmolCheckbox> | |||
<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/gd/2gdn_consurf.spt"</scriptWhenChecked> | |||
<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | |||
<text>to colour the structure by Evolutionary Conservation</text> | |||
</jmolCheckbox> | |||
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2gdn ConSurf]. | |||
<div style="clear:both"></div> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
beta-Lactam antibiotics are extremely effective in disrupting the synthesis of the bacterial cell wall in both gram-positive and gram-negative bacteria. However, they are ineffective against Mycobacterium tuberculosis, due to the production of a beta-lactamase enzyme encoded on the chromosome of M. tuberculosis that degrades these antibiotics. Indeed, recent studies have demonstrated that deletion of the blaC gene, the only gene encoding a beta-lactamase in M. tuberculosis, or inhibition of the encoded enzyme resulted in significantly increased sensitivity to beta-lactam antibiotics. In this paper we present a biochemical and structural characterization of M. tuberculosis BlaC. Recombinant BlaC shows a broad range of specificity with almost equal penicillinase and cepholothinase activity. While clavulanate is a mechanism-based inhibitor to class A beta-lactamase with high potency (typically K(i) < 0.1 microM), it is a relatively poor inhibitor of the M. tuberculosis BlaC (K(i) = 2.4 microM). The crystal structure of the enzyme, determined at a resolution of 1.7 A, shows that the overall fold of the M. tuberculosis enzyme is similar to other class A beta-lactamases. There are, however, several distinct features of the active site, such as the amino acid substitutions N132G, R164A, R244A, and R276E, that explain the broad specificity of the enzyme, relatively low penicillinase activity, and resistance to clavulanate. | |||
Crystal structure and activity studies of the Mycobacterium tuberculosis beta-lactamase reveal its critical role in resistance to beta-lactam antibiotics.,Wang F, Cassidy C, Sacchettini JC Antimicrob Agents Chemother. 2006 Aug;50(8):2762-71. PMID:16870770<ref>PMID:16870770</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 2gdn" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
== | [[Category: Large Structures]] | ||
== | |||
[[Category: | |||
[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: | [[Category: Cassidy C]] | ||
[[Category: | [[Category: Sacchettini JC]] | ||
[[Category: | [[Category: Wang F]] | ||
Latest revision as of 12:39, 30 August 2023
Crystal structure of the Mycobacterium tuberculosis beta-lactamaseCrystal structure of the Mycobacterium tuberculosis beta-lactamase
Structural highlights
FunctionEvolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedbeta-Lactam antibiotics are extremely effective in disrupting the synthesis of the bacterial cell wall in both gram-positive and gram-negative bacteria. However, they are ineffective against Mycobacterium tuberculosis, due to the production of a beta-lactamase enzyme encoded on the chromosome of M. tuberculosis that degrades these antibiotics. Indeed, recent studies have demonstrated that deletion of the blaC gene, the only gene encoding a beta-lactamase in M. tuberculosis, or inhibition of the encoded enzyme resulted in significantly increased sensitivity to beta-lactam antibiotics. In this paper we present a biochemical and structural characterization of M. tuberculosis BlaC. Recombinant BlaC shows a broad range of specificity with almost equal penicillinase and cepholothinase activity. While clavulanate is a mechanism-based inhibitor to class A beta-lactamase with high potency (typically K(i) < 0.1 microM), it is a relatively poor inhibitor of the M. tuberculosis BlaC (K(i) = 2.4 microM). The crystal structure of the enzyme, determined at a resolution of 1.7 A, shows that the overall fold of the M. tuberculosis enzyme is similar to other class A beta-lactamases. There are, however, several distinct features of the active site, such as the amino acid substitutions N132G, R164A, R244A, and R276E, that explain the broad specificity of the enzyme, relatively low penicillinase activity, and resistance to clavulanate. Crystal structure and activity studies of the Mycobacterium tuberculosis beta-lactamase reveal its critical role in resistance to beta-lactam antibiotics.,Wang F, Cassidy C, Sacchettini JC Antimicrob Agents Chemother. 2006 Aug;50(8):2762-71. PMID:16870770[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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