3hlg
From Proteopedia
(Difference between revisions)
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<StructureSection load='3hlg' size='340' side='right'caption='[[3hlg]], [[Resolution|resolution]] 2.01Å' scene=''> | <StructureSection load='3hlg' size='340' side='right'caption='[[3hlg]], [[Resolution|resolution]] 2.01Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[3hlg]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/ | + | <table><tr><td colspan='2'>[[3hlg]] is a 1 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=3HLG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HLG FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LVA:(3R,5R)-7-((1R,2R,6S,8R,8AS)-2,6-DIMETHYL-8-{[(2R)-2-METHYLBUTANOYL]OXY}-1,2,6,7,8,8A-HEXAHYDRONAPHTHALEN-1-YL)-3,5-DIHYDROXYHEPTANOIC+ACID'>LVA</scene | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.01Å</td></tr> |
| - | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=LVA:(3R,5R)-7-((1R,2R,6S,8R,8AS)-2,6-DIMETHYL-8-{[(2R)-2-METHYLBUTANOYL]OXY}-1,2,6,7,8,8A-HEXAHYDRONAPHTHALEN-1-YL)-3,5-DIHYDROXYHEPTANOIC+ACID'>LVA</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=3hlg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hlg OCA], [https://pdbe.org/3hlg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hlg RCSB], [https://www.ebi.ac.uk/pdbsum/3hlg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hlg 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=3hlg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hlg OCA], [https://pdbe.org/3hlg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hlg RCSB], [https://www.ebi.ac.uk/pdbsum/3hlg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hlg ProSAT]</span></td></tr> | ||
</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> | ||
== Evolutionary Conservation == | == Evolutionary Conservation == | ||
[[Image:Consurf_key_small.gif|200px|right]] | [[Image:Consurf_key_small.gif|200px|right]] | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Aspergillus terreus]] |
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
| - | [[Category: Gao | + | [[Category: Gao X]] |
| - | [[Category: Pashkov | + | [[Category: Pashkov I]] |
| - | [[Category: Sawaya | + | [[Category: Sawaya MR]] |
| - | [[Category: Tang | + | [[Category: Tang Y]] |
| - | [[Category: Yeates | + | [[Category: Yeates TO]] |
| - | + | ||
| - | + | ||
Current revision
Simvastatin Synthase (LovD), from Aspergillus terreus, S5 mutant, S76A mutant, complex with lovastatin
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