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.

5e5l

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 17:01, 15 November 2017

Crystal structure of Mycobacterium tuberculosis L,D-transpeptidase 1 at 1.89 Angstrom

Structural highlights

5e5l is a 4 chain structure with sequence from Myctu. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	5du7, 5duj, 5dvp, 5dvq, 5dwt, 5dzj, 5dzp, 5e1g, 5e1i, 5e51
Gene:	ldtA, Rv0116c, RVBD_0116c, P425_00122 (MYCTU)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[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.^[1] ^[2]

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Lavollay M, Arthur M, Fourgeaud M, Dubost L, Marie A, Veziris N, Blanot D, Gutmann L, Mainardi JL. The peptidoglycan of stationary-phase Mycobacterium tuberculosis predominantly contains cross-links generated by L,D-transpeptidation. J Bacteriol. 2008 Jun;190(12):4360-6. doi: 10.1128/JB.00239-08. Epub 2008 Apr 11. PMID:18408028 doi:http://dx.doi.org/10.1128/JB.00239-08
↑ Cordillot M, Dubee V, Triboulet S, Dubost L, Marie A, Hugonnet JE, Arthur M, Mainardi JL. In vitro cross-linking of Mycobacterium tuberculosis peptidoglycan by L,D-transpeptidases and inactivation of these enzymes by carbapenems. Antimicrob Agents Chemother. 2013 Dec;57(12):5940-5. doi: 10.1128/AAC.01663-13., Epub 2013 Sep 16. PMID:24041897 doi:http://dx.doi.org/10.1128/AAC.01663-13
↑ 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. Non-classical transpeptidases yield insight into new antibacterials. Nat Chem Biol. 2016 Nov 7. doi: 10.1038/nchembio.2237. PMID:27820797 doi:http://dx.doi.org/10.1038/nchembio.2237

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/5e5l"

@@ Line 3: / Line 3: @@
 <StructureSection load='5e5l' size='340' side='right' caption='[[5e5l]], [[Resolution|resolution]] 1.89&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[5e5l]] is a 4 chain structure. 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 [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>
 </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>
+<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'>[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>
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
+[[Category: Myctu]]
 [[Category: Ginell, S L]]
 [[Category: Kumar, P]]

5e5l

From Proteopedia

Revision as of 17:01, 15 November 2017

Crystal structure of Mycobacterium tuberculosis L,D-transpeptidase 1 at 1.89 Angstrom

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox