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7f71

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Current revision

Crystal structure of the Mycobacterium tuberculosis L,D-transpeptidase-2 (LdtMt2) with peptidoglycan sugar moiety and glutamate

Structural highlights

7f71 is a 2 chain structure with sequence from Mycobacterium tuberculosis H37Rv. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.58Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1]

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.

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^[2]

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

References

↑ 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
↑ Ahmad N, Dugad S, Chauhan V, Ahmed S, Sharma K, Kachhap S, Zaidi R, Bishai WR, Lamichhane G, Kumar P. Allosteric cooperation in beta-lactam binding to a non-classical transpeptidase. Elife. 2022 Apr 27;11. pii: 73055. doi: 10.7554/eLife.73055. PMID:35475970 doi:http://dx.doi.org/10.7554/eLife.73055

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/7f71"

Categories: Large Structures | Mycobacterium tuberculosis H37Rv | Kumar P | Lamichhane G

@@ Line 3: / Line 3: @@
 <StructureSection load='7f71' size='340' side='right'caption='[[7f71]], [[Resolution|resolution]] 1.58&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[7f71]] is a 2 chain structure. 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='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>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.58&#8491;</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>
 == 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>
+[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 ==
@@ Line 23: / Line 24: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Kumar, P]]
+[[Category: Mycobacterium tuberculosis H37Rv]]
-[[Category: Lamichhane, G]]
+[[Category: Kumar P]]
-[[Category: Cysteine protease]]
+[[Category: Lamichhane G]]
-[[Category: D-transpeptidase]]
-[[Category: Hydrolase]]

7f71

From Proteopedia

Current revision

Crystal structure of the Mycobacterium tuberculosis L,D-transpeptidase-2 (LdtMt2) with peptidoglycan sugar moiety and glutamate

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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