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4lcm
From Proteopedia
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==Simvastatin Synthase (LOVD), from Aspergillus Terreus, LovD9 mutant (simh9014)== | ==Simvastatin Synthase (LOVD), from Aspergillus Terreus, LovD9 mutant (simh9014)== | ||
| - | <StructureSection load='4lcm' size='340' side='right' caption='[[4lcm]], [[Resolution|resolution]] 3.19Å' scene=''> | + | <StructureSection load='4lcm' size='340' side='right'caption='[[4lcm]], [[Resolution|resolution]] 3.19Å' scene=''> |
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[4lcm]] is a 4 chain structure with sequence from [ | + | <table><tr><td colspan='2'>[[4lcm]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_terreus Aspergillus terreus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LCM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LCM FirstGlance]. <br> |
| - | </td></tr><tr><td class="sblockLbl"><b>[[ | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.19Å</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=4lcm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lcm OCA], [https://pdbe.org/4lcm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lcm RCSB], [https://www.ebi.ac.uk/pdbsum/4lcm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lcm ProSAT]</span></td></tr> | |
| - | <tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | </table> |
| - | <table> | + | == Function == |
| + | [https://www.uniprot.org/uniprot/LOVD_ASPTE LOVD_ASPTE] Monacolin J acid methylbutanoyltransferase; part of the gene cluster that mediates the biosynthesis of lovastatin (also known as mevinolin, mevacor or monacolin K), a hypolipidemic inhibitor of (3S)-hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase (HMGR) (PubMed:10334994, PubMed:12929390, PubMed:21495633). The first step in the biosynthesis of lovastatin is the production of dihydromonacolin L acid by the lovastatin nonaketide synthase lovB and the trans-acting enoyl reductase lovC via condensation of one acetyl-CoA unit and 8 malonyl-CoA units (PubMed:10334994, PubMed:10381407, PubMed:19900898, PubMed:22733743). Dihydromonacolin L acid is released from lovB by the thioesterase lovG (PubMed:23653178). Next, dihydromonacolin L acid is oxidized by the dihydromonacolin L monooxygenase lovA twice to form monacolin J acid (PubMed:12929390, PubMed:21495633). The 2-methylbutyrate moiety of lovastatin is synthesized by the lovastatin diketide synthase lovF via condensation of one acetyl-CoA unit and one malonyl-CoA unit (PubMed:19530726, PubMed:21069965). Finally, the covalent attachment of this moiety to monacolin J acid is catalyzed by the transesterase lovD to yield lovastatin (PubMed:10334994, PubMed:17113998, PubMed:18988191, PubMed:19875080, PubMed:24727900). LovD has broad substrate specificity and can also convert monacolin J to simvastatin using alpha-dimethylbutanoyl-S-methyl-3-mercaptopropionate (DMB-S-MMP) as the thioester acyl donor, and can also catalyze the reverse reaction and function as hydrolase in vitro (PubMed:19875080). LovD has much higher activity with LovF-bound 2-methylbutanoate than with free diketide substrates (PubMed:21069965).<ref>PMID:10334994</ref> <ref>PMID:10381407</ref> <ref>PMID:12929390</ref> <ref>PMID:17113998</ref> <ref>PMID:18988191</ref> <ref>PMID:19530726</ref> <ref>PMID:19875080</ref> <ref>PMID:19900898</ref> <ref>PMID:21069965</ref> <ref>PMID:21495633</ref> <ref>PMID:22733743</ref> <ref>PMID:23653178</ref> <ref>PMID:24727900</ref> | ||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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The role of distant mutations and allosteric regulation on LovD active site dynamics.,Jimenez-Oses G, Osuna S, Gao X, Sawaya MR, Gilson L, Collier SJ, Huisman GW, Yeates TO, Tang Y, Houk KN Nat Chem Biol. 2014 Jun;10(6):431-6. doi: 10.1038/nchembio.1503. Epub 2014 Apr, 13. PMID:24727900<ref>PMID:24727900</ref> | The role of distant mutations and allosteric regulation on LovD active site dynamics.,Jimenez-Oses G, Osuna S, Gao X, Sawaya MR, Gilson L, Collier SJ, Huisman GW, Yeates TO, Tang Y, Houk KN Nat Chem Biol. 2014 Jun;10(6):431-6. doi: 10.1038/nchembio.1503. Epub 2014 Apr, 13. PMID:24727900<ref>PMID:24727900</ref> | ||
| - | From | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
</div> | </div> | ||
| + | <div class="pdbe-citations 4lcm" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[Simvastatin Synthase|Simvastatin Synthase]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Aspergillus terreus]] |
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: | + | [[Category: Gao X]] |
| - | [[Category: | + | [[Category: Sawaya MR]] |
| - | [[Category: | + | [[Category: Tang Y]] |
| - | [[Category: | + | [[Category: Yeates TO]] |
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Current revision
Simvastatin Synthase (LOVD), from Aspergillus Terreus, LovD9 mutant (simh9014)
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