+Open data
-Basic information
Entry | Database: PDB / ID: 7cpx | ||||||
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Title | Lovastatin nonaketide synthase | ||||||
Components | Lovastatin nonaketide synthase, polyketide synthase component | ||||||
Keywords | BIOSYNTHETIC PROTEIN / polyketide synthase | ||||||
Function / homology | Function and homology information malonyl-CoA metabolic process / lovastatin nonaketide synthase / lovastatin nonaketide synthase activity / lovastatin biosynthetic process / polyketide synthase activity / NADPH oxidation / polyketide biosynthetic process / S-adenosylmethionine metabolic process / S-adenosylmethionine-dependent methyltransferase activity / fatty acid synthase activity ...malonyl-CoA metabolic process / lovastatin nonaketide synthase / lovastatin nonaketide synthase activity / lovastatin biosynthetic process / polyketide synthase activity / NADPH oxidation / polyketide biosynthetic process / S-adenosylmethionine metabolic process / S-adenosylmethionine-dependent methyltransferase activity / fatty acid synthase activity / acyltransferase activity, transferring groups other than amino-acyl groups / phosphopantetheine binding / 3-oxoacyl-[acyl-carrier-protein] synthase activity / fatty acid biosynthetic process / methylation / oxidoreductase activity / ATP binding Similarity search - Function | ||||||
Biological species | Aspergillus terreus (mold) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.91 Å | ||||||
Authors | Wang, J. / Wang, Z. | ||||||
Funding support | China, 1items
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Citation | Journal: Nat Commun / Year: 2021 Title: Structural basis for the biosynthesis of lovastatin. Authors: Jialiang Wang / Jingdan Liang / Lu Chen / Wei Zhang / Liangliang Kong / Chao Peng / Chen Su / Yi Tang / Zixin Deng / Zhijun Wang / Abstract: 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), ...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 Å and the core LovB at 2.91 Å 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. | ||||||
History |
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-Structure visualization
Movie |
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Structure viewer | Molecule: MolmilJmol/JSmol |
-Downloads & links
-Download
PDBx/mmCIF format | 7cpx.cif.gz | 1.4 MB | Display | PDBx/mmCIF format |
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PDB format | pdb7cpx.ent.gz | 1.2 MB | Display | PDB format |
PDBx/mmJSON format | 7cpx.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7cpx_validation.pdf.gz | 1.3 MB | Display | wwPDB validaton report |
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Full document | 7cpx_full_validation.pdf.gz | 1.3 MB | Display | |
Data in XML | 7cpx_validation.xml.gz | 125.6 KB | Display | |
Data in CIF | 7cpx_validation.cif.gz | 190.1 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/cp/7cpx ftp://data.pdbj.org/pub/pdb/validation_reports/cp/7cpx | HTTPS FTP |
-Related structure data
Related structure data | 30434MC 7cpyC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 336446.656 Da / Num. of mol.: 2 / Mutation: G1884Q, Q1885A Source method: isolated from a genetically manipulated source Source: (gene. exp.) Aspergillus terreus (mold) / Gene: lovB / Production host: Saccharomyces cerevisiae (brewer's yeast) / References: UniProt: Q9Y8A5, lovastatin nonaketide synthase #2: Chemical | Has ligand of interest | Y | |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Lovastatin nonaketide synthase / Type: COMPLEX / Entity ID: #1 / Source: RECOMBINANT |
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Molecular weight | Value: 335 kDa/nm / Experimental value: YES |
Source (natural) | Organism: Aspergillus terreus (mold) |
Source (recombinant) | Organism: Saccharomyces cerevisiae (brewer's yeast) |
Buffer solution | pH: 8 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES / Details: This sample was homogenous |
Specimen support | Grid material: COPPER / Grid type: Quantifoil R1.2/1.3 |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD |
Specimen holder | Cryogen: NITROGEN / Specimen holder model: FEI TITAN KRIOS AUTOGRID HOLDER |
Image recording | Electron dose: 60.8 e/Å2 / Film or detector model: GATAN K2 SUMMIT (4k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.16_3549: / Classification: refinement | ||||||||||||||||||||||||
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EM software |
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CTF correction | Type: NONE | ||||||||||||||||||||||||
Symmetry | Point symmetry: C2 (2 fold cyclic) | ||||||||||||||||||||||||
3D reconstruction | Resolution: 2.91 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 205047 / Symmetry type: POINT | ||||||||||||||||||||||||
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