4g2r
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4g2r]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G2R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4G2R FirstGlance]. <br> | <table><tr><td colspan='2'>[[4g2r]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4G2R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4G2R FirstGlance]. <br> | ||
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=H1L:(2R)-2-(4-{[3-CHLORO-5-(TRIFLUOROMETHYL)PYRIDIN-2-YL]OXY}PHENOXY)PROPANOIC+ACID'>H1L</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]] 2.28Å</td></tr> |
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=H1L:(2R)-2-(4-{[3-CHLORO-5-(TRIFLUOROMETHYL)PYRIDIN-2-YL]OXY}PHENOXY)PROPANOIC+ACID'>H1L</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=4g2r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g2r OCA], [https://pdbe.org/4g2r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4g2r RCSB], [https://www.ebi.ac.uk/pdbsum/4g2r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4g2r 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=4g2r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4g2r OCA], [https://pdbe.org/4g2r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4g2r RCSB], [https://www.ebi.ac.uk/pdbsum/4g2r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4g2r ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/ACCD6_MYCTU ACCD6_MYCTU] Component of a biotin-dependent acyl-CoA carboxylase complex. This subunit transfers the CO2 from carboxybiotin to the CoA ester substrate (PubMed:17114269). When associated with the alpha3 subunit AccA3, is involved in the carboxylation of acetyl-CoA and propionyl-CoA, with a preference for acetyl-CoA (PubMed:17114269).<ref>PMID:17114269</ref> | [https://www.uniprot.org/uniprot/ACCD6_MYCTU ACCD6_MYCTU] Component of a biotin-dependent acyl-CoA carboxylase complex. This subunit transfers the CO2 from carboxybiotin to the CoA ester substrate (PubMed:17114269). When associated with the alpha3 subunit AccA3, is involved in the carboxylation of acetyl-CoA and propionyl-CoA, with a preference for acetyl-CoA (PubMed:17114269).<ref>PMID:17114269</ref> | ||
| - | <div style="background-color:#fffaf0;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | In Mycobacterium tuberculosis (Mtb) the carboxylation of acetyl-CoA to produce malonyl-CoA, a building block in long chain fatty acid biosynthesis, is catalyzed by two enzymes working sequentially: a biotin carboxylase (AccA), and a carboxyltransferase (AccD). While the exact roles of the three different biotin carboxylases (AccA1-3) and the six carboxyltransferases (AccD1-6) in Mtb are still not clear, AccD6 in complex with AccA3 can synthesize malonyl-CoA from acetyl-CoA. A series of ten herbicides that target plant acetyl-CoA carboxylases (ACC) were tested for inhibition of AccD6 and for whole-cell activity against Mtb. From the tested herbicides, haloxyfop, an arylophenoxypropionate, showed in vitro inhibition of Mtb AccD6, with an IC50 = 21.4 +/- 1 muM. Here, we report the crystal structures of Mtb AccD6 in the apo form (3.0 A) and in complex with haloxyfop-R (2.3 A). The structure of Mtb AccD6 in complex with haloxyfop-R shows two molecules of the inhibitor bound on each AccD6 subunit. These results represent the potential for developing novel therapeutics for tuberculosis based on herbicides with low human toxicity. | ||
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| - | Structure, Activity, and Inhibition of the Carboxyltransferase beta-subunit of Acetyl-CoA Carboxylase (AccD6) from Mycobacterium tuberculosis.,Reddy MC, Breda A, Bruning JB, Sherekar M, Valluru S, Thurman C, Ehrenfeld H, Sacchettini JC Antimicrob Agents Chemother. 2014 Aug 4. pii: AAC.02574-13. PMID:25092705<ref>PMID:25092705</ref> | ||
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 4g2r" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
Crystal Structure of the carboxyltransferase subunit of ACC (AccD6) in complex with inhibitor haloxyfop from Mycobacterium tuberculosis
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