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5e51

From Proteopedia

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Current revision

Crystal structure of Mycobacterium tuberculosis L,D-transpeptidase 1 with Faropenem adduct

Structural highlights

5e51 is a 4 chain structure with sequence from Mycobacterium tuberculosis CDC1551. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.25Å
Ligands:
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/5e51"

Categories: Large Structures | Mycobacterium tuberculosis CDC1551 | Ginell SL | Kumar P | Lamichhane G

@@ Line 1: / Line 1: @@
 ==Crystal structure of Mycobacterium tuberculosis L,D-transpeptidase 1 with Faropenem adduct==
-<StructureSection load='5e51' size='340' side='right' caption='[[5e51]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
+<StructureSection load='5e51' size='340' side='right'caption='[[5e51]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
 == 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 [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5E51 FirstGlance]. <br>
+<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]] 2.25&#8491;</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=5e51 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5e51 OCA], [http://pdbe.org/5e51 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5e51 RCSB], [http://www.ebi.ac.uk/pdbsum/5e51 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5e51 ProSAT]</span></td></tr>
+<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>
 == Function ==
-[[http://www.uniprot.org/uniprot/LDT1_MYCTO LDT1_MYCTO]] 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 (By similarity).
+[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 ==
@@ Line 22: / Line 23: @@
 __TOC__
 </StructureSection>
-[[Category: Ginell, S L]]
+[[Category: Large Structures]]
-[[Category: Kumar, P]]
+[[Category: Mycobacterium tuberculosis CDC1551]]
-[[Category: Lamichhane, G]]
+[[Category: Ginell SL]]
-[[Category: Cell wall enzyme]]
+[[Category: Kumar P]]
-[[Category: D-transpeptidase 1]]
+[[Category: Lamichhane G]]
-[[Category: Ldtmt1]]
-[[Category: Mycobacterium tuberculosis]]
-[[Category: Peptidoglycan synthesis enzyme]]
-[[Category: Transferase]]

5e51

From Proteopedia

Current revision

Crystal structure of Mycobacterium tuberculosis L,D-transpeptidase 1 with Faropenem adduct

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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