View source for 6d4k


==Crystal structure of L,D-transpeptidase 3 from Mycobacterium tuberculosis at 1.32 A resolution==
<StructureSection load='6d4k' size='340' side='right'caption='[[6d4k]], [[Resolution|resolution]] 1.32&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[6d4k]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_H37Rv Mycobacterium tuberculosis H37Rv]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D4K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6D4K 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]] 1.32&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</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=6d4k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d4k OCA], [https://pdbe.org/6d4k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6d4k RCSB], [https://www.ebi.ac.uk/pdbsum/6d4k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6d4k ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LDT3_MYCTU LDT3_MYCTU] Probable L,D-transpeptidase that may perform as-yet-unknown cross-linking reactions in M.tuberculosis. Is not able to generate 3->3 cross-links in peptidoglycan, using tetrapeptide stems as acyl donor substrates. May function in the anchoring of proteins to peptidoglycan.<ref>PMID:24041897</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Targeting Mycobacterium tuberculosis peptidoglycans with beta-lactam antibiotics represents a strategy to address increasing resistance to antitubercular drugs. beta-Lactams inhibit peptidoglycan synthases such as l,d-transpeptidases, a group of carbapenem-sensitive enzymes that stabilize peptidoglycans through 3 --&gt; 3 cross-links. M. tuberculosis encodes five l,d-transpeptidases (LdtMt1-5), of which LdtMt3 is one of the less understood. Herein, we structurally characterized the apo and faropenem-acylated forms of LdtMt3 at 1.3 and 1.8 A resolution, respectively. These structures revealed a fold and catalytic diad similar to those of other LdtsMt enzymes, supporting its involvement in transpeptidation reactions despite divergences in active site size and charges. The LdtMt3-faropenem structure indicated that faropenem is degraded after Cys-246 acylation, and possibly only a beta-OH-butyrate or an acetyl group (C2H3O) covalently attached to the enzyme remains, an observation that strongly supports the notion that LdtMt3 is inactivated by beta-lactams. Docking simulations with intact beta-lactams predicted key LdtMt3 residues that interact with these antibiotics. We also characterized the heat of acylation involved in the binding and reaction of LdtMt3 for ten beta-lactams belonging to four different classes, and imipenem had the highest inactivation constant. This work provides key insights into the structure, binding mechanisms, and degradation of beta-lactams by LdtMt3, which may be useful for the development of additional beta-lactams with potential antitubercular activity.

Structural Basis for the Interaction and Processing of beta-Lactam Antibiotics by l,d-Transpeptidase 3 (LdtMt3) from Mycobacterium tuberculosis.,Libreros-Zuniga GA, Dos Santos Silva C, Salgado Ferreira R, Dias MVB ACS Infect Dis. 2019 Feb 8;5(2):260-271. doi: 10.1021/acsinfecdis.8b00244. Epub, 2018 Dec 28. PMID:30556998<ref>PMID:30556998</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 6d4k" style="background-color:#fffaf0;"></div>
== References ==
<references/>
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</StructureSection>
[[Category: Large Structures]]
[[Category: Mycobacterium tuberculosis H37Rv]]
[[Category: Dias MVB]]
[[Category: Libreros GA]]