7f71
From Proteopedia
(Difference between revisions)
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==Crystal structure of the Mycobacterium tuberculosis L,D-transpeptidase-2 (LdtMt2) with peptidoglycan sugar moiety and glutamate== | ==Crystal structure of the Mycobacterium tuberculosis L,D-transpeptidase-2 (LdtMt2) with peptidoglycan sugar moiety and glutamate== | ||
| - | <StructureSection load='7f71' size='340' side='right'caption='[[7f71]]' scene=''> | + | <StructureSection load='7f71' size='340' side='right'caption='[[7f71]], [[Resolution|resolution]] 1.58Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7F71 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7F71 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7f71]] is a 2 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=7F71 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7F71 FirstGlance]. <br> |
| - | </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=7f71 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7f71 OCA], [https://pdbe.org/7f71 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7f71 RCSB], [https://www.ebi.ac.uk/pdbsum/7f71 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7f71 ProSAT]</span></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.58Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BGC:BETA-D-GLUCOSE'>BGC</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=7f71 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7f71 OCA], [https://pdbe.org/7f71 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7f71 RCSB], [https://www.ebi.ac.uk/pdbsum/7f71 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7f71 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/LDT2_MYCTU LDT2_MYCTU] Generates 3->3 cross-links in peptidoglycan, catalyzing the cleavage of the mDap(3)-D-Ala(4) bond of a tetrapeptide donor stem and the formation of a bond between the carbonyl of mDap(3) of the donor stem and the side chain of mDap(3) of the acceptor stem. Is specific for donor substrates containing a stem tetrapeptide since it cannot use pentapeptide stems.<ref>PMID:24041897</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | L,D-transpeptidase function predominates in atypical 3 --> 3 transpeptide networking of peptidoglycan (PG) layer in Mycobacterium tuberculosis. Prior studies of L,D-transpeptidases have identified only the catalytic site that binds to peptide moiety of the PG substrate or beta-lactam antibiotics. This insight was leveraged to develop mechanism of its activity and inhibition by beta-lactams. Here, we report identification of an allosteric site at a distance of 21 A from the catalytic site that binds the sugar moiety of PG substrates (hereafter referred to as the S-pocket). This site also binds a second beta-lactam molecule and influences binding at the catalytic site. We provide evidence that two beta-lactam molecules bind co-operatively to this enzyme, one non-covalently at the S-pocket and one covalently at the catalytic site. This dual beta-lactam-binding phenomenon is previously unknown and is an observation that may offer novel approaches for the structure-based design of new drugs against M. tuberculosis. | ||
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| + | Allosteric cooperation in beta-lactam binding to a non-classical transpeptidase.,Ahmad N, Dugad S, Chauhan V, Ahmed S, Sharma K, Kachhap S, Zaidi R, Bishai WR, Lamichhane G, Kumar P Elife. 2022 Apr 27;11. pii: 73055. doi: 10.7554/eLife.73055. PMID:35475970<ref>PMID:35475970</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 7f71" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| + | [[Category: Mycobacterium tuberculosis H37Rv]] | ||
[[Category: Kumar P]] | [[Category: Kumar P]] | ||
[[Category: Lamichhane G]] | [[Category: Lamichhane G]] | ||
Current revision
Crystal structure of the Mycobacterium tuberculosis L,D-transpeptidase-2 (LdtMt2) with peptidoglycan sugar moiety and glutamate
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