7cpy

From Proteopedia

(Difference between revisions)

Current revision

Lovastatin nonaketide synthase with LovC

Structural highlights

7cpy is a 4 chain structure with sequence from Aspergillus terreus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.6Å
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

LOVC_ASPTE Catalyzes the NADPH-dependent reduction of the unsaturated tetra-, penta- and heptaketide intermediates that arise during the LovB-mediated biosynthesis of the lovastatin nonaketide chain.^[1] ^[2] ^[3]

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^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Kennedy J, Auclair K, Kendrew SG, Park C, Vederas JC, Hutchinson CR. Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis. Science. 1999 May 21;284(5418):1368-72. PMID:10334994
↑ Ma SM, Li JW, Choi JW, Zhou H, Lee KK, Moorthie VA, Xie X, Kealey JT, Da Silva NA, Vederas JC, Tang Y. Complete reconstitution of a highly reducing iterative polyketide synthase. Science. 2009 Oct 23;326(5952):589-92. doi: 10.1126/science.1175602. PMID:19900898 doi:http://dx.doi.org/10.1126/science.1175602
↑ Ames BD, Nguyen C, Bruegger J, Smith P, Xu W, Ma S, Wong E, Wong S, Xie X, Li JW, Vederas JC, Tang Y, Tsai SC. Crystal structure and biochemical studies of the trans-acting polyketide enoyl reductase LovC from lovastatin biosynthesis. Proc Natl Acad Sci U S A. 2012 Jun 25. PMID:22733743 doi:10.1073/pnas.1113029109
↑ Wang J, Liang J, Chen L, Zhang W, Kong L, Peng C, Su C, Tang Y, Deng Z, Wang Z. Structural basis for the biosynthesis of lovastatin. Nat Commun. 2021 Feb 8;12(1):867. doi: 10.1038/s41467-021-21174-8. PMID:33558520 doi:http://dx.doi.org/10.1038/s41467-021-21174-8

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7cpy"

Categories: Aspergillus terreus | Large Structures | Wang J | Wang Z

@@ Line 1: / Line 1: @@
-'''Unreleased structure'''
-The entry 7cpy is ON HOLD
+==Lovastatin nonaketide synthase with LovC==
+<StructureSection load='7cpy' size='340' side='right'caption='[[7cpy]], [[Resolution|resolution]] 3.60&Aring;' scene=''>
+== Structural highlights ==
+<table><tr><td colspan='2'>[[7cpy]] 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=7CPY OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CPY FirstGlance]. <br>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.6&#8491;</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7cpy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cpy OCA], [https://pdbe.org/7cpy PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cpy RCSB], [https://www.ebi.ac.uk/pdbsum/7cpy PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cpy ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/LOVC_ASPTE LOVC_ASPTE] Catalyzes the NADPH-dependent reduction of the unsaturated tetra-, penta- and heptaketide intermediates that arise during the LovB-mediated biosynthesis of the lovastatin nonaketide chain.<ref>PMID:10334994</ref> <ref>PMID:19900898</ref> <ref>PMID:22733743</ref>
+<div style="background-color:#fffaf0;">
+== 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.
-Authors: Wang, J.L., Wang, Z.J.
+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>
-Description: Lovastatin nonaketide synthase with LovC
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-[[Category: Unreleased Structures]]
+</div>
-[[Category: Wang, Z.J]]
+<div class="pdbe-citations 7cpy" style="background-color:#fffaf0;"></div>
-[[Category: Wang, J.L]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
+[[Category: Aspergillus terreus]]
+[[Category: Large Structures]]
+[[Category: Wang J]]
+[[Category: Wang Z]]

7cpy

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Current revision

Lovastatin nonaketide synthase with LovC

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

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