4jd6: Difference between revisions

Revision as of 11:06, 24 November 2022

Crystal structure of Mycobacterium tuberculosis Eis in complex with coenzyme A and tobramycin

Structural highlights

4jd6 is a 6 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.
Ligands:	COA, TOY
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

A recently discovered cause of tuberculosis resistance to a drug of last resort, the aminoglycoside kanamycin, results from modification of this drug by the enhanced intracellular survival (Eis) protein. Eis is a structurally and functionally unique acetyltransferase with an unusual capability of acetylating aminoglycosides at multiple positions. The extent of this regioversatility and its defining protein features are unclear. Herein, we determined the positions and order of acetylation of five aminoglycosides by NMR spectroscopy. This analysis revealed unprecedented acetylation of the 3-amine of kanamycin, amikacin, and tobramycin, and the gamma-amine of the 4-amino-2-hydroxybutyryl group of amikacin. A crystal structure of Eis in complex with coenzyme A and tobramycin revealed how tobramycin can be accommodated in the Eis active site in two binding modes, consistent with its diacetylation. These studies, describing chemical and structural details of acetylation, will guide future efforts towards designing aminoglycosides and Eis inhibitors to overcome resistance in tuberculosis.

Chemical and Structural Insights into the Regioversatility of the Aminoglycoside Acetyltransferase Eis.,Houghton JL, Biswas T, Chen W, Tsodikov OV, Garneau-Tsodikova S Chembiochem. 2013 Sep 17. doi: 10.1002/cbic.201300359. PMID:24106131^[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
↑ Houghton JL, Biswas T, Chen W, Tsodikov OV, Garneau-Tsodikova S. Chemical and Structural Insights into the Regioversatility of the Aminoglycoside Acetyltransferase Eis. Chembiochem. 2013 Sep 17. doi: 10.1002/cbic.201300359. PMID:24106131 doi:https://dx.doi.org/10.1002/cbic.201300359

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OCA

[1] 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

[2] Houghton JL, Biswas T, Chen W, Tsodikov OV, Garneau-Tsodikova S. Chemical and Structural Insights into the Regioversatility of the Aminoglycoside Acetyltransferase Eis. Chembiochem. 2013 Sep 17. doi: 10.1002/cbic.201300359. PMID:24106131 doi:https://dx.doi.org/10.1002/cbic.201300359

[1]

[2]

@@ Line 1: / Line 1: @@
 ==Crystal structure of Mycobacterium tuberculosis Eis in complex with coenzyme A and tobramycin==
-<StructureSection load='4jd6' size='340' side='right' caption='[[4jd6]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
+<StructureSection load='4jd6' size='340' side='right'caption='[[4jd6]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4jd6]] is a 6 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=4JD6 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4JD6 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4jd6]] is a 6 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=4JD6 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4JD6 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=TOY:TOBRAMYCIN'>TOY</scene></td></tr>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=COA:COENZYME+A'>COA</scene>, <scene name='pdbligand=TOY:TOBRAMYCIN'>TOY</scene></td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">RVBD_2416c ([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'>[https://proteopedia.org/fgij/fg.htm?mol=4jd6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jd6 OCA], [https://pdbe.org/4jd6 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4jd6 RCSB], [https://www.ebi.ac.uk/pdbsum/4jd6 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4jd6 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=4jd6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4jd6 OCA], [http://pdbe.org/4jd6 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4jd6 RCSB], [http://www.ebi.ac.uk/pdbsum/4jd6 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4jd6 ProSAT]</span></td></tr>
 </table>
+== Function ==
+[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 21: / Line 22: @@
 __TOC__
 </StructureSection>
-[[Category: Myctu]]
+[[Category: Large Structures]]
-[[Category: Biswas, T]]
+[[Category: Mycobacterium tuberculosis H37Rv]]
-[[Category: Chen, W]]
+[[Category: Biswas T]]
-[[Category: Garneau-Tsodikova, S]]
+[[Category: Chen W]]
-[[Category: Tsodikov, O V]]
+[[Category: Garneau-Tsodikova S]]
-[[Category: Aminoglycoside acetyltransferase]]
+[[Category: Tsodikov OV]]
-[[Category: Gnat]]
-[[Category: Transferase]]

4jd6: Difference between revisions

Revision as of 11:06, 24 November 2022

Crystal structure of Mycobacterium tuberculosis Eis in complex with coenzyme A and tobramycin

Structural highlights

Function

Publication Abstract from PubMed

References

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