This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.
Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.
6d51
From Proteopedia
(Difference between revisions)
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of L,D-transpeptidase 3 from Mycobacterium tuberculosis in complex with a faropenem-derived adduct== | |
| + | <StructureSection load='6d51' size='340' side='right' caption='[[6d51]], [[Resolution|resolution]] 1.83Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6d51]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6D51 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6D51 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ACE:ACETYL+GROUP'>ACE</scene>, <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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6d51 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6d51 OCA], [http://pdbe.org/6d51 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6d51 RCSB], [http://www.ebi.ac.uk/pdbsum/6d51 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6d51 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [[http://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 --> 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®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6d51" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Dias, M V.B]] | ||
| + | [[Category: Libreros, G A]] | ||
| + | [[Category: Adduct]] | ||
| + | [[Category: Transferase]] | ||
Revision as of 15:16, 27 February 2019
Crystal structure of L,D-transpeptidase 3 from Mycobacterium tuberculosis in complex with a faropenem-derived adduct
| |||||||||||
