5e51
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==Crystal structure of Mycobacterium tuberculosis L,D-transpeptidase 1 with Faropenem adduct== | ==Crystal structure of Mycobacterium tuberculosis L,D-transpeptidase 1 with Faropenem adduct== | ||
| - | <StructureSection load='5e51' size='340' side='right' caption='[[5e51]], [[Resolution|resolution]] 2.25Å' scene=''> | + | <StructureSection load='5e51' size='340' side='right'caption='[[5e51]], [[Resolution|resolution]] 2.25Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[5e51]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E51 OCA]. For a <b>guided tour on the structure components</b> use [ | + | <table><tr><td colspan='2'>[[5e51]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis_CDC1551 Mycobacterium tuberculosis CDC1551]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E51 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5E51 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5KO:(3R)-3-HYDROXYBUTANAL'>5KO</scene></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]] 2.25Å</td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5KO:(3R)-3-HYDROXYBUTANAL'>5KO</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=5e51 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e51 OCA], [https://pdbe.org/5e51 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5e51 RCSB], [https://www.ebi.ac.uk/pdbsum/5e51 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5e51 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
| - | [ | + | [https://www.uniprot.org/uniprot/LDT1_MYCTU LDT1_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. Is thought to play a role in adaptation to the nonreplicative state of M.tuberculosis.<ref>PMID:18408028</ref> <ref>PMID:24041897</ref> |
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Bacterial survival requires an intact peptidoglycan layer, a three-dimensional exoskeleton that encapsulates the cytoplasmic membrane. Historically, the final steps of peptidoglycan synthesis are known to be carried out by D,D-transpeptidases, enzymes that are inhibited by the beta-lactams, which constitute >50% of all antibacterials in clinical use. Here, we show that the carbapenem subclass of beta-lactams are distinctly effective not only because they inhibit D,D-transpeptidases and are poor substrates for beta-lactamases, but primarily because they also inhibit non-classical transpeptidases, namely the L,D-transpeptidases, which generate the majority of linkages in the peptidoglycan of mycobacteria. We have characterized the molecular mechanisms responsible for inhibition of L,D-transpeptidases of Mycobacterium tuberculosis and a range of bacteria including ESKAPE pathogens, and used this information to design, synthesize and test simplified carbapenems with potent antibacterial activity. | ||
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| + | Non-classical transpeptidases yield insight into new antibacterials.,Kumar P, Kaushik A, Lloyd EP, Li SG, Mattoo R, Ammerman NC, Bell DT, Perryman AL, Zandi TA, Ekins S, Ginell SL, Townsend CA, Freundlich JS, Lamichhane G Nat Chem Biol. 2016 Nov 7. doi: 10.1038/nchembio.2237. PMID:27820797<ref>PMID:27820797</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5e51" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Mycobacterium tuberculosis CDC1551]] |
| - | [[Category: | + | [[Category: Ginell SL]] |
| - | [[Category: | + | [[Category: Kumar P]] |
| - | [[Category: | + | [[Category: Lamichhane G]] |
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Current revision
Crystal structure of Mycobacterium tuberculosis L,D-transpeptidase 1 with Faropenem adduct
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