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==Cryo-EM structure of Mycobacterium smegmatis arabinosyltransferase EmbC2-AcpM2 in complex with ethambutol== | ==Cryo-EM structure of Mycobacterium smegmatis arabinosyltransferase EmbC2-AcpM2 in complex with ethambutol== | ||
<StructureSection load='7bve' size='340' side='right'caption='[[7bve]]' scene=''> | <StructureSection load='7bve' size='340' side='right'caption='[[7bve]], [[Resolution|resolution]] 2.81Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BVE OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7BVE FirstGlance]. <br> | <table><tr><td colspan='2'>[[7bve]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Mycs2 Mycs2] and [http://en.wikipedia.org/wiki/Mycolicibacterium_smegmatis_mc2_155 Mycolicibacterium smegmatis mc2 155]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7BVE OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=7BVE FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7bve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bve OCA], [http://pdbe.org/7bve PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7bve RCSB], [http://www.ebi.ac.uk/pdbsum/7bve PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7bve ProSAT]</span></td></tr> | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=95E:Ethambutol'>95E</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=PN7:N~3~-[(2S)-2-HYDROXY-3,3-DIMETHYL-4-(PHOSPHONOOXY)BUTANOYL]-N-(2-SULFANYLETHYL)-BETA-ALANINAMIDE'>PN7</scene>, <scene name='pdbligand=PO4:PHOSPHATE+ION'>PO4</scene></td></tr> | ||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">embC, MSMEI_6219 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=246196 MYCS2])</td></tr> | |||
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Indolylacetylinositol_arabinosyltransferase Indolylacetylinositol arabinosyltransferase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.4.2.34 2.4.2.34] </span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7bve FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7bve OCA], [http://pdbe.org/7bve PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7bve RCSB], [http://www.ebi.ac.uk/pdbsum/7bve PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7bve ProSAT]</span></td></tr> | |||
</table> | </table> | ||
== Function == | |||
[[http://www.uniprot.org/uniprot/ACPM_MYCS2 ACPM_MYCS2]] Acyl carrier protein involved in meromycolate extension. | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The arabinosyltransferases EmbA, EmbB, and EmbC are involved in Mycobacterium tuberculosis cell wall synthesis and are recognized as the targets for the anti-tuberculosis drug ethambutol. We have determined cryo-electron microscopy and x-ray crystal structures of mycobacterial EmbA-EmbB and EmbC-EmbC complexes, in the presence of their glycosyl donor and acceptor substrates and with ethambutol. These structures show how the donor and acceptor substrates bind in the active site and how ethambutol inhibits by binding to the same site as both substrates in EmbB and EmbC. The majority of drug-resistant mutations are located nearby to the ethambutol-binding site. Collectively, our work provides a structural basis for understanding the biochemical function and inhibition of arabinosyltransferases and development of new anti-tuberculosis agents. | |||
Structures of cell wall arabinosyltransferases with the anti-tuberculosis drug ethambutol.,Zhang L, Zhao Y, Gao Y, Wu L, Gao R, Zhang Q, Wang Y, Wu C, Wu F, Gurcha SS, Veerapen N, Batt SM, Zhao W, Qin L, Yang X, Wang M, Zhu Y, Zhang B, Bi L, Zhang X, Yang H, Guddat LW, Xu W, Wang Q, Li J, Besra GS, Rao Z Science. 2020 Apr 23. pii: science.aba9102. doi: 10.1126/science.aba9102. PMID:32327601<ref>PMID:32327601</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7bve" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Indolylacetylinositol arabinosyltransferase]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Besra | [[Category: Mycolicibacterium smegmatis mc2 155]] | ||
[[Category: Gao Y]] | [[Category: Mycs2]] | ||
[[Category: Li J]] | [[Category: Besra, G S]] | ||
[[Category: Rao Z]] | [[Category: Gao, Y]] | ||
[[Category: Wang Q]] | [[Category: Li, J]] | ||
[[Category: Zhang L]] | [[Category: Rao, Z]] | ||
[[Category: Zhao Y]] | [[Category: Wang, Q]] | ||
[[Category: Zhang, L]] | |||
[[Category: Zhao, Y]] | |||
[[Category: Acyl carrier protein]] | |||
[[Category: Arabinogalactan]] | |||
[[Category: Arabinosyltransferase]] | |||
[[Category: Cell wall synthesis]] | |||
[[Category: Drug resistance]] | |||
[[Category: Drug target]] | |||
[[Category: Embc]] | |||
[[Category: Ethambutol]] | |||
[[Category: Lipoarabinomannan]] | |||
[[Category: Mycobacterium smegmati]] | |||
[[Category: Transferase]] | |||