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Yorodumi- PDB-6nna: Human Fatty Acid Synthase Psi/KR Tri-Domain with NADPH and Compound 22 -
+Open data
-Basic information
Entry | Database: PDB / ID: 6nna | ||||||
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Title | Human Fatty Acid Synthase Psi/KR Tri-Domain with NADPH and Compound 22 | ||||||
Components | Fatty acid synthase,Fatty acid synthase | ||||||
Keywords | TRANSFERASE / FATTY ACID SYNTHASE / HUMAN FAS / KETO-REDUCTASE | ||||||
Function / homology | Function and homology information fatty-acid synthase system / : / : / : / ether lipid biosynthetic process / Vitamin B5 (pantothenate) metabolism / : / neutrophil differentiation / enoyl-[acyl-carrier-protein] reductase (NADPH, Re-specific) / glandular epithelial cell development ...fatty-acid synthase system / : / : / : / ether lipid biosynthetic process / Vitamin B5 (pantothenate) metabolism / : / neutrophil differentiation / enoyl-[acyl-carrier-protein] reductase (NADPH, Re-specific) / glandular epithelial cell development / glycogen granule / establishment of endothelial intestinal barrier / [acyl-carrier-protein] S-acetyltransferase / [acyl-carrier-protein] S-acetyltransferase activity / : / oleoyl-[acyl-carrier-protein] hydrolase / Fatty acyl-CoA biosynthesis / fatty acyl-[ACP] hydrolase activity / modulation by host of viral process / enoyl-[acyl-carrier-protein] reductase (NADPH) activity / ChREBP activates metabolic gene expression / [acyl-carrier-protein] S-malonyltransferase / [acyl-carrier-protein] S-malonyltransferase activity / 3-hydroxyacyl-[acyl-carrier-protein] dehydratase / beta-ketoacyl-[acyl-carrier-protein] synthase I / mammary gland development / NR1H2 & NR1H3 regulate gene expression linked to lipogenesis / 3-oxoacyl-[acyl-carrier-protein] reductase / 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity / fatty acid synthase activity / phosphopantetheine binding / monocyte differentiation / 3-oxoacyl-[acyl-carrier-protein] synthase activity / cellular response to interleukin-4 / Activation of gene expression by SREBF (SREBP) / fatty acid metabolic process / fatty acid biosynthetic process / osteoblast differentiation / melanosome / inflammatory response / cadherin binding / Golgi apparatus / RNA binding / extracellular exosome / membrane / plasma membrane / cytosol / cytoplasm Similarity search - Function | ||||||
Biological species | Homo sapiens (human) | ||||||
Method | X-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 2.26 Å | ||||||
Authors | Toms, A.V. / Martin, M.W. | ||||||
Citation | Journal: Bioorg. Med. Chem. Lett. / Year: 2019 Title: Discovery and optimization of novel piperazines as potent inhibitors of fatty acid synthase (FASN). Authors: Martin, M.W. / Lancia Jr., D.R. / Li, H. / Schiller, S.E.R. / Toms, A.V. / Wang, Z. / Bair, K.W. / Castro, J. / Fessler, S. / Gotur, D. / Hubbs, S.E. / Kauffman, G.S. / Kershaw, M. / Luke, G. ...Authors: Martin, M.W. / Lancia Jr., D.R. / Li, H. / Schiller, S.E.R. / Toms, A.V. / Wang, Z. / Bair, K.W. / Castro, J. / Fessler, S. / Gotur, D. / Hubbs, S.E. / Kauffman, G.S. / Kershaw, M. / Luke, G.P. / McKinnon, C. / Yao, L. / Lu, W. / Millan, D.S. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 6nna.cif.gz | 265.3 KB | Display | PDBx/mmCIF format |
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PDB format | pdb6nna.ent.gz | 207.4 KB | Display | PDB format |
PDBx/mmJSON format | 6nna.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 6nna_validation.pdf.gz | 1.6 MB | Display | wwPDB validaton report |
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Full document | 6nna_full_validation.pdf.gz | 1.6 MB | Display | |
Data in XML | 6nna_validation.xml.gz | 50.4 KB | Display | |
Data in CIF | 6nna_validation.cif.gz | 72.2 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/nn/6nna ftp://data.pdbj.org/pub/pdb/validation_reports/nn/6nna | HTTPS FTP |
-Related structure data
Related structure data | 4pivS S: Starting model for refinement |
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Similar structure data |
-Links
-Assembly
Deposited unit |
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1 |
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2 |
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Unit cell |
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-Components
#1: Protein | Mass: 71965.102 Da / Num. of mol.: 2 / Mutation: M1110Q,S1438A,P1524G,M1110Q,S1438A,P1524G Source method: isolated from a genetically manipulated source Source: (gene. exp.) Homo sapiens (human) / Gene: FASN, FAS / Production host: Spodoptera frugiperda (fall armyworm) References: UniProt: P49327, fatty-acid synthase system, [acyl-carrier-protein] S-acetyltransferase, [acyl-carrier-protein] S-malonyltransferase, beta-ketoacyl-[acyl-carrier-protein] synthase I, 3- ...References: UniProt: P49327, fatty-acid synthase system, [acyl-carrier-protein] S-acetyltransferase, [acyl-carrier-protein] S-malonyltransferase, beta-ketoacyl-[acyl-carrier-protein] synthase I, 3-oxoacyl-[acyl-carrier-protein] reductase, 3-hydroxyacyl-[acyl-carrier-protein] dehydratase, enoyl-[acyl-carrier-protein] reductase (NADPH, Re-specific), oleoyl-[acyl-carrier-protein] hydrolase #2: Chemical | #3: Chemical | #4: Chemical | ChemComp-EDO / #5: Water | ChemComp-HOH / | |
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-Experimental details
-Experiment
Experiment | Method: X-RAY DIFFRACTION / Number of used crystals: 1 |
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-Sample preparation
Crystal | Density Matthews: 2.26 Å3/Da / Density % sol: 45.48 % |
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Crystal grow | Temperature: 291 K / Method: vapor diffusion, hanging drop / pH: 7.6 Details: 0.19 M ammonium sulfate, 5 mM sodium cacodylate,pH7.6 and 27 % w/v PEG 3350 |
-Data collection
Diffraction | Mean temperature: 100 K / Serial crystal experiment: N |
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Diffraction source | Source: SYNCHROTRON / Site: SSRF / Beamline: BL18U1 / Wavelength: 0.97853 Å |
Detector | Type: DECTRIS PILATUS3 S 6M / Detector: PIXEL / Date: Dec 21, 2018 |
Radiation | Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray |
Radiation wavelength | Wavelength: 0.97853 Å / Relative weight: 1 |
Reflection | Resolution: 2.26→48.08 Å / Num. obs: 57291 / % possible obs: 97.3 % / Redundancy: 1.8 % / CC1/2: 0.988 / Rmerge(I) obs: 0.065 / Rpim(I) all: 0.065 / Rrim(I) all: 0.093 / Net I/σ(I): 6.6 |
Reflection shell | Resolution: 2.26→2.32 Å / Redundancy: 1.8 % / Rmerge(I) obs: 0.344 / Num. unique obs: 4419 / CC1/2: 0.712 / Rpim(I) all: 0.344 / Rrim(I) all: 0.487 / % possible all: 96.1 |
-Phasing
Phasing | Method: molecular replacement |
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-Processing
Software |
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Refinement | Method to determine structure: MOLECULAR REPLACEMENT Starting model: 4piv Resolution: 2.26→48.08 Å / Cor.coef. Fo:Fc: 0.94 / Cor.coef. Fo:Fc free: 0.899 / SU B: 7.655 / SU ML: 0.187 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.392 / ESU R Free: 0.25 Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
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Solvent computation | Ion probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Displacement parameters | Biso max: 123.42 Å2 / Biso mean: 34.873 Å2 / Biso min: 12.41 Å2
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Refinement step | Cycle: final / Resolution: 2.26→48.08 Å
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Refine LS restraints |
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LS refinement shell | Resolution: 2.26→2.319 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
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