|
|
| (One intermediate revision not shown.) |
| Line 1: |
Line 1: |
| | | | |
| | ==Crystal structure of Mycobacterium tuberculosis L,D-transpeptidase 1 at 1.89 Angstrom== | | ==Crystal structure of Mycobacterium tuberculosis L,D-transpeptidase 1 at 1.89 Angstrom== |
| - | <StructureSection load='5e5l' size='340' side='right' caption='[[5e5l]], [[Resolution|resolution]] 1.89Å' scene=''> | + | <StructureSection load='5e5l' size='340' side='right'caption='[[5e5l]], [[Resolution|resolution]] 1.89Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5e5l]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Myctu Myctu]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5E5L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5E5L FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5e5l]] is a 4 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=5E5L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5E5L FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5du7|5du7]], [[5duj|5duj]], [[5dvp|5dvp]], [[5dvq|5dvq]], [[5dwt|5dwt]], [[5dzj|5dzj]], [[5dzp|5dzp]], [[5e1g|5e1g]], [[5e1i|5e1i]], [[5e51|5e51]]</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]] 1.89Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ldtA, Rv0116c, RVBD_0116c, P425_00122 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</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=5e5l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e5l OCA], [https://pdbe.org/5e5l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5e5l RCSB], [https://www.ebi.ac.uk/pdbsum/5e5l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5e5l ProSAT]</span></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=5e5l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e5l OCA], [http://pdbe.org/5e5l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e5l RCSB], [http://www.ebi.ac.uk/pdbsum/5e5l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5e5l ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://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> | + | [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.
| + | |
| - | | + | |
| - | 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>
| + | |
| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 5e5l" style="background-color:#fffaf0;"></div>
| + | |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Myctu]] | + | [[Category: Large Structures]] |
| - | [[Category: Ginell, S L]] | + | [[Category: Mycobacterium tuberculosis H37Rv]] |
| - | [[Category: Kumar, P]] | + | [[Category: Ginell SL]] |
| - | [[Category: Lamichhane, G]] | + | [[Category: Kumar P]] |
| - | [[Category: Cell wall enzyme]] | + | [[Category: Lamichhane G]] |
| - | [[Category: Peptidoglycan synthesis enzyme]]
| + | |
| - | [[Category: Transferase]]
| + | |
