6rrm: Difference between revisions

Revision as of 20:37, 12 April 2023

Crystal structure of LdtMt2 from Mycobacterium tuberculosis bound to Ebselen

Structural highlights

6rrm is a 2 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.
Ligands:	9JT, EDO, GOL, NH4
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

The l,d-transpeptidases (Ldts) are promising antibiotic targets for treating tuberculosis. We report screening of cysteine-reactive inhibitors against LdtMt2 from Mycobacterium tuberculosis. Structural studies on LdtMt2 with potent inhibitor ebselen reveal opening of the benzisoselenazolone ring by a nucleophilic cysteine, forming a complex involving extensive hydrophobic interactions with a substrate-binding loop.

Targeting the Mycobacterium tuberculosis transpeptidase LdtMt2 with cysteine-reactive inhibitors including ebselen.,de Munnik M, Lohans CT, Lang PA, Langley GW, Malla TR, Tumber A, Schofield CJ, Brem J Chem Commun (Camb). 2019 Aug 5. doi: 10.1039/c9cc04145a. PMID:31380528^[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:https://dx.doi.org/10.1128/AAC.01663-13
↑ de Munnik M, Lohans CT, Lang PA, Langley GW, Malla TR, Tumber A, Schofield CJ, Brem J. Targeting the Mycobacterium tuberculosis transpeptidase LdtMt2 with cysteine-reactive inhibitors including ebselen. Chem Commun (Camb). 2019 Aug 5. doi: 10.1039/c9cc04145a. PMID:31380528 doi:https://dx.doi.org/10.1039/c9cc04145a

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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:https://dx.doi.org/10.1128/AAC.01663-13

[2] Munnik M, Lohans CT, Lang PA, Langley GW, Malla TR, Tumber A, Schofield CJ, Brem J. Targeting the Mycobacterium tuberculosis transpeptidase LdtMt2 with cysteine-reactive inhibitors including ebselen. Chem Commun (Camb). 2019 Aug 5. doi: 10.1039/c9cc04145a. PMID:31380528 doi:https://dx.doi.org/10.1039/c9cc04145a

[1]

[2]

@@ Line 3: / Line 3: @@
 <StructureSection load='6rrm' size='340' side='right'caption='[[6rrm]], [[Resolution|resolution]] 1.64&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6rrm]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycto Mycto]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6RRM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6RRM FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6rrm]] is a 2 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=6RRM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6RRM FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=9JT:~{N}-phenyl-2-selanyl-benzamide'>9JT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NH4:AMMONIUM+ION'>NH4</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=9JT:N-phenyl-2-selanylbenzamide'>9JT</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NH4:AMMONIUM+ION'>NH4</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">ldtB, MT2594, V735_02606 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83331 MYCTO])</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=6rrm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rrm OCA], [https://pdbe.org/6rrm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6rrm RCSB], [https://www.ebi.ac.uk/pdbsum/6rrm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6rrm 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=6rrm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6rrm OCA], [http://pdbe.org/6rrm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6rrm RCSB], [http://www.ebi.ac.uk/pdbsum/6rrm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6rrm ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/LDT2_MYCTO LDT2_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. Is essential for virulence in a mouse model of acute infection.<ref>PMID:20305661</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 24: / Line 23: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Mycto]]
+[[Category: Mycobacterium tuberculosis CDC1551]]
-[[Category: Brem, J]]
+[[Category: Brem J]]
-[[Category: Lohans, C]]
+[[Category: Lohans C]]
-[[Category: Schofield, C]]
+[[Category: Schofield C]]
-[[Category: Antibiotic resistance]]
-[[Category: Antimicrobial protein]]
-[[Category: Beta lactmase]]
-[[Category: Tuberculosis]]

6rrm: Difference between revisions

Revision as of 20:37, 12 April 2023

Crystal structure of LdtMt2 from Mycobacterium tuberculosis bound to Ebselen

Structural highlights

Function

Publication Abstract from PubMed

References

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