7cpx

<table><tr><td colspan='2'>[[7cpx]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspte Aspte]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CPX OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CPX FirstGlance]. <br>

</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr>

<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">lovB ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=33178 ASPTE])</td></tr>

<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Lovastatin_nonaketide_synthase Lovastatin nonaketide synthase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.3.1.161 2.3.1.161] </span></td></tr>

== Function ==

[[https://www.uniprot.org/uniprot/LOVB_ASPTE LOVB_ASPTE]] Lovastatin nonaketide synthase; 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, PubMed:23023987). 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:23023987, 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:23023987</ref> <ref>PMID:23653178</ref> <ref>PMID:24727900</ref>

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== Publication Abstract from PubMed ==

Statins are effective cholesterol-lowering drugs. Lovastatin, one of the precursors of statins, is formed from dihydromonacolin L (DML), which is synthesized by lovastatin nonaketide synthase (LovB), with the assistance of a separate trans-acting enoyl reductase (LovC). A full DML synthesis comprises 8 polyketide synthetic cycles with about 35 steps. The assembling of the LovB-LovC complex, and the structural basis for the iterative and yet permutative functions of the megasynthase have remained a mystery. Here, we present the cryo-EM structures of the LovB-LovC complex at 3.60 A and the core LovB at 2.91 A resolution. The domain organization of LovB is an X-shaped face-to-face dimer containing eight connected domains. The binding of LovC laterally to the malonyl-acetyl transferase domain allows the completion of a L-shaped catalytic chamber consisting of six active domains. This architecture and the structural details of the megasynthase provide the basis for the processing of the intermediates by the individual catalytic domains. The detailed architectural model provides structural insights that may enable the re-engineering of the megasynthase for the generation of new statins.

Structural basis for the biosynthesis of lovastatin.,Wang J, Liang J, Chen L, Zhang W, Kong L, Peng C, Su C, Tang Y, Deng Z, Wang Z Nat Commun. 2021 Feb 8;12(1):867. doi: 10.1038/s41467-021-21174-8. PMID:33558520<ref>PMID:33558520</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>

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<div class="pdbe-citations 7cpx" style="background-color:#fffaf0;"></div>

== References ==

<references/>

[[Category: Aspte]]

[[Category: Wang, J]]

[[Category: Wang, Z]]

[[Category: Polyketide synthase]]