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6p3v

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Current revision

Crystal structure of Eis from Mycobacterium tuberculosis in complex with inhibitor SGT416

Structural highlights

6p3v is a 1 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 2.5Å
Ligands:	, ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

EIS_MYCTU May participate in pathogenesis, possibly by enhancing survival of the bacteria in host macrophages during infection.^[1]

Publication Abstract from PubMed

Each year, millions of people worldwide contract tuberculosis (TB), the deadliest infection. The spread of infections with drug-resistant strains of Mycobacterium tuberculosis (Mtb) that are refractory to treatment poses a major global challenge. A major cause of resistance to antitubercular drugs of last resort, aminoglycosides, is overexpression of the Eis (enhanced intracellular survival) enzyme of Mtb, which inactivates aminoglycosides by acetylating them. We showed previously that this inactivation of aminoglycosides could be overcome by our recently reported Eis inhibitors that are currently in development as potential aminoglycoside adjunctive therapeutics against drug-resistant TB. To interrogate the robustness of the Eis inhibitors, we investigated the enzymatic activity of Eis and its inhibition by Eis inhibitors from three different structural families for nine single-residue mutants of Eis, including those found in the clinic. Three engineered mutations of the substrate binding site, D26A, W36A, and F84A, abolished inhibitor binding while compromising Eis enzymatic activity 2- to 3-fold. All other Eis mutants, including clinically observed ones, were potently inhibited by at least one inhibitor. This study helps position us one step ahead of Mtb resistance to Eis inhibitors as they are being developed for TB therapy.

Probing the Robustness of Inhibitors of Tuberculosis Aminoglycoside Resistance Enzyme Eis by Mutagenesis.,Green KD, Punetha A, Hou C, Garneau-Tsodikova S, Tsodikov OV ACS Infect Dis. 2019 Oct 11;5(10):1772-1778. doi: 10.1021/acsinfecdis.9b00228., Epub 2019 Aug 21. PMID:31433614^[2]

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

References

↑ Wei J, Dahl JL, Moulder JW, Roberts EA, O'Gaora P, Young DB, Friedman RL. Identification of a Mycobacterium tuberculosis gene that enhances mycobacterial survival in macrophages. J Bacteriol. 2000 Jan;182(2):377-84. PMID:10629183
↑ Green KD, Punetha A, Hou C, Garneau-Tsodikova S, Tsodikov OV. Probing the Robustness of Inhibitors of Tuberculosis Aminoglycoside Resistance Enzyme Eis by Mutagenesis. ACS Infect Dis. 2019 Oct 11;5(10):1772-1778. doi: 10.1021/acsinfecdis.9b00228., Epub 2019 Aug 21. PMID:31433614 doi:http://dx.doi.org/10.1021/acsinfecdis.9b00228

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/6p3v"

Categories: Large Structures | Mycobacterium tuberculosis H37Rv | Garneau-Tsodikova S | Punetha A | Tsodikov OV

@@ Line 3: / Line 3: @@
 <StructureSection load='6p3v' size='340' side='right'caption='[[6p3v]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6p3v]] is a 1 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=6P3V OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6P3V FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6p3v]] is a 1 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=6P3V OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6P3V FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NRV:N,N-diethyl-2-[(8-fluoro-5-methyl-5H-[1,2,4]triazino[5,6-b]indol-3-yl)sulfanyl]ethan-1-amine'>NRV</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 2.5&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">eis, Rv2416c, MTCY253.04 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=83332 MYCTU])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=DMS:DIMETHYL+SULFOXIDE'>DMS</scene>, <scene name='pdbligand=NRV:N,N-diethyl-2-[(8-fluoro-5-methyl-5H-[1,2,4]triazino[5,6-b]indol-3-yl)sulfanyl]ethan-1-amine'>NRV</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></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=6p3v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p3v OCA], [http://pdbe.org/6p3v PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6p3v RCSB], [http://www.ebi.ac.uk/pdbsum/6p3v PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6p3v ProSAT]</span></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=6p3v FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6p3v OCA], [https://pdbe.org/6p3v PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6p3v RCSB], [https://www.ebi.ac.uk/pdbsum/6p3v PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6p3v ProSAT]</span></td></tr>
 </table>
 == Function ==
-[[http://www.uniprot.org/uniprot/EIS_MYCTU EIS_MYCTU]] May participate in pathogenesis, possibly by enhancing survival of the bacteria in host macrophages during infection.<ref>PMID:10629183</ref>
+[https://www.uniprot.org/uniprot/EIS_MYCTU EIS_MYCTU] May participate in pathogenesis, possibly by enhancing survival of the bacteria in host macrophages during infection.<ref>PMID:10629183</ref>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 24: / Line 24: @@
 </StructureSection>
 [[Category: Large Structures]]
-[[Category: Myctu]]
+[[Category: Mycobacterium tuberculosis H37Rv]]
-[[Category: Garneau-Tsodikova, S]]
+[[Category: Garneau-Tsodikova S]]
-[[Category: Punetha, A]]
+[[Category: Punetha A]]
-[[Category: Tsodikov, O V]]
+[[Category: Tsodikov OV]]
-[[Category: Acetyltransferase]]
-[[Category: Aminoglycoside resistance]]
-[[Category: Competitive inhibitor]]
-[[Category: Transferase]]
-[[Category: Transferase-transferase inhibitor complex]]

6p3v

From Proteopedia

Current revision

Crystal structure of Eis from Mycobacterium tuberculosis in complex with inhibitor SGT416

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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