3hlf: Difference between revisions
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<StructureSection load='3hlf' size='340' side='right'caption='[[3hlf]], [[Resolution|resolution]] 2.00Å' scene=''> | <StructureSection load='3hlf' size='340' side='right'caption='[[3hlf]], [[Resolution|resolution]] 2.00Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3hlf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/ | <table><tr><td colspan='2'>[[3hlf]] 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=3HLF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3HLF FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2Å</td></tr> | ||
<tr id=' | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SIM:SIMVASTATIN+ACID'>SIM</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=3hlf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hlf OCA], [https://pdbe.org/3hlf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hlf RCSB], [https://www.ebi.ac.uk/pdbsum/3hlf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hlf 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=3hlf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3hlf OCA], [https://pdbe.org/3hlf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3hlf RCSB], [https://www.ebi.ac.uk/pdbsum/3hlf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3hlf 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]] | ||