[English] 日本語
Yorodumi
- PDB-7mhe: Thioesterase Domain of Human Fatty Acid Synthase (FASN-TE) bindin... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7mhe
TitleThioesterase Domain of Human Fatty Acid Synthase (FASN-TE) binding a competitive inhibitor SBP-7957
ComponentsFatty acid synthase
KeywordsHYDROLASE/Inhibitor / THIOESTERASE DOMAIN / FATTY ACID SYNTHASE / FASN-TE / HYDROLASE-Inhibitor complex
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 / NR1H2 & NR1H3 regulate gene expression linked to lipogenesis / mammary gland development / 3-oxoacyl-[acyl-carrier-protein] reductase / 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity / fatty acid synthase activity / monocyte differentiation / phosphopantetheine binding / 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 / cadherin binding / inflammatory response / Golgi apparatus / RNA binding / extracellular exosome / membrane / plasma membrane / cytosol / cytoplasm
Similarity search - Function
: / Fatty acid synthase, pseudo-KR domain / Methyltransferase type 12 / Methyltransferase domain / Thioesterase / Thioesterase domain / Polyketide synthase, dehydratase domain / PKS_DH / : / Polyketide synthase dehydratase domain ...: / Fatty acid synthase, pseudo-KR domain / Methyltransferase type 12 / Methyltransferase domain / Thioesterase / Thioesterase domain / Polyketide synthase, dehydratase domain / PKS_DH / : / Polyketide synthase dehydratase domain / Polyketide synthase, dehydratase domain superfamily / : / Polyketide and metazoan fatty acid synthase dehydratase (PKS/mFAS DH) domain profile. / Polyketide synthase, C-terminal extension / Ketoacyl-synthetase C-terminal extension / Polyketide synthase, ketoreductase domain / KR domain / Malonyl-CoA ACP transacylase, ACP-binding / : / Acyl transferase / Acyl transferase domain / Acyl transferase domain in polyketide synthase (PKS) enzymes. / Alcohol dehydrogenase-like, C-terminal / Acyl transferase domain superfamily / Zinc-binding dehydrogenase / Acyl transferase/acyl hydrolase/lysophospholipase / Polyketide synthase, enoylreductase domain / Enoylreductase / Polyketide synthase, phosphopantetheine-binding domain / Phosphopantetheine attachment site / Beta-ketoacyl synthase / Beta-ketoacyl synthase, active site / Ketosynthase family 3 (KS3) active site signature. / PKS_KR / Ketosynthase family 3 (KS3) domain profile. / Beta-ketoacyl synthase, N-terminal / Beta-ketoacyl synthase, C-terminal / Polyketide synthase, beta-ketoacyl synthase domain / Beta-ketoacyl synthase, N-terminal domain / Beta-ketoacyl synthase, C-terminal domain / GroES-like superfamily / Thiolase-like / Phosphopantetheine attachment site / Phosphopantetheine attachment site. / Phosphopantetheine attachment site / ACP-like superfamily / Carrier protein (CP) domain profile. / Phosphopantetheine binding ACP domain / Alpha/Beta hydrolase fold / NAD(P)-binding domain superfamily / S-adenosyl-L-methionine-dependent methyltransferase superfamily
Similarity search - Domain/homology
Chem-ZEG / Fatty acid synthase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.8 Å
AuthorsAleshin, A.E. / Lambert, L. / Liddington, R.C. / Cosford, N.
CitationJournal: To Be Published
Title: Thioesterase Domain of Human Fatty Acid Synthase (FASN-TE) binding a competitive inhibitor SBP-7635
Authors: Aleshin, A.E. / Lambert, L. / Liddington, R.C. / Cosford, N.
History
DepositionApr 15, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 20, 2022Provider: repository / Type: Initial release
Revision 1.1Oct 18, 2023Group: Data collection / Derived calculations / Refinement description
Category: atom_type / chem_comp_atom ...atom_type / chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model
Item: _atom_type.pdbx_N_electrons / _atom_type.pdbx_scat_Z

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
AAA: Fatty acid synthase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)32,9913
Polymers32,5251
Non-polymers4672
Water27015
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)52.680, 56.500, 75.640
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Fatty acid synthase / Type I fatty acid synthase


Mass: 32524.670 Da / Num. of mol.: 1 / Fragment: Thioesterase
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: FASN, FAS / Production host: Escherichia coli (E. coli)
References: UniProt: P49327, oleoyl-[acyl-carrier-protein] hydrolase
#2: Chemical ChemComp-ZEG / 4-{4-[2-(4-fluorophenyl)-1,3-thiazol-4-yl]benzene-1-sulfonyl}morpholine


Mass: 404.478 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C19H17FN2O3S2 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-EDO / 1,2-ETHANEDIOL / ETHYLENE GLYCOL


Mass: 62.068 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6O2
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 15 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 1.73 Å3/Da / Density % sol: 28.92 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: 0.3 uL of 8 mg/ml FAS-TE in 100 mM NaCl, 50 mM BisTris pH 6.0, 10 mM DTT, 0.5 mM of the inhibitor and 1% DMSO was mixed with 0.2 uL of well solution 10% PEG400, 50 mM Tris-Cl pH 8.5, 1.0 mM ...Details: 0.3 uL of 8 mg/ml FAS-TE in 100 mM NaCl, 50 mM BisTris pH 6.0, 10 mM DTT, 0.5 mM of the inhibitor and 1% DMSO was mixed with 0.2 uL of well solution 10% PEG400, 50 mM Tris-Cl pH 8.5, 1.0 mM DTT, 1.0 mM Ethylenediaminetetraacetic acid disodium salt (EDTA), 300 mM NaCl.
PH range: 6.0-8.5

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL9-2 / Wavelength: 1.03316 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Feb 9, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.03316 Å / Relative weight: 1
ReflectionResolution: 2.8→45.3 Å / Num. obs: 5295 / % possible obs: 90.7 % / Redundancy: 4.6 % / Rmerge(I) obs: 0.2 / Net I/σ(I): 5.2
Reflection shellResolution: 2.8→2.9 Å / Rmerge(I) obs: 1.19 / Mean I/σ(I) obs: 1.4 / Num. unique obs: 759

-
Processing

Software
NameVersionClassification
REFMAC5.8.0257refinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3TJM

3tjm


Resolution: 2.8→37.849 Å / Cor.coef. Fo:Fc: 0.939 / Cor.coef. Fo:Fc free: 0.876 / SU B: 25.392 / SU ML: 0.469 / Cross valid method: THROUGHOUT / ESU R Free: 0.558
Details: Hydrogens have been added in their riding positions
RfactorNum. reflection% reflection
Rfree0.2836 291 5.496 %
Rwork0.2132 5004 -
all0.217 --
obs-5295 89.473 %
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK BULK SOLVENT
Displacement parametersBiso mean: 59.85 Å2
Baniso -1Baniso -2Baniso -3
1-2.675 Å20 Å20 Å2
2--2.409 Å20 Å2
3----5.085 Å2
Refinement stepCycle: LAST / Resolution: 2.8→37.849 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2165 0 31 15 2211
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0080.0132244
X-RAY DIFFRACTIONr_bond_other_d0.0010.0172051
X-RAY DIFFRACTIONr_ext_dist_refined_d0.0720.013474
X-RAY DIFFRACTIONr_angle_refined_deg1.4941.663045
X-RAY DIFFRACTIONr_angle_other_deg1.3031.5754758
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.455276
X-RAY DIFFRACTIONr_dihedral_angle_2_deg36.60721.826115
X-RAY DIFFRACTIONr_dihedral_angle_3_deg17.16415365
X-RAY DIFFRACTIONr_dihedral_angle_4_deg14.8321515
X-RAY DIFFRACTIONr_chiral_restr0.0740.2288
X-RAY DIFFRACTIONr_gen_planes_refined0.0080.022505
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02472
X-RAY DIFFRACTIONr_nbd_refined0.2170.2524
X-RAY DIFFRACTIONr_symmetry_nbd_other0.1820.22060
X-RAY DIFFRACTIONr_nbtor_refined0.1680.21101
X-RAY DIFFRACTIONr_symmetry_nbtor_other0.0820.21082
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1760.265
X-RAY DIFFRACTIONr_symmetry_nbd_refined0.2150.238
X-RAY DIFFRACTIONr_nbd_other0.2240.2122
X-RAY DIFFRACTIONr_symmetry_xyhbond_nbd_refined0.2360.23
X-RAY DIFFRACTIONr_mcbond_it3.3346.3361110
X-RAY DIFFRACTIONr_mcbond_other3.3336.3351109
X-RAY DIFFRACTIONr_mcangle_it5.3429.4971384
X-RAY DIFFRACTIONr_mcangle_other5.349.4991385
X-RAY DIFFRACTIONr_scbond_it3.1236.6661134
X-RAY DIFFRACTIONr_scbond_other3.1226.6651135
X-RAY DIFFRACTIONr_scangle_it5.2469.8731661
X-RAY DIFFRACTIONr_scangle_other5.2459.8721662
X-RAY DIFFRACTIONr_lrange_it11.22120.6439641
X-RAY DIFFRACTIONr_lrange_other11.22120.6459641
LS refinement shellResolution: 2.8→2.872 Å
RfactorNum. reflection% reflection
Rfree0.42 23 -
Rwork0.303 373 -
obs--94.2857 %

+
About Yorodumi

-
News

-
Feb 9, 2022. New format data for meta-information of EMDB entries

New format data for meta-information of EMDB entries

  • Version 3 of the EMDB header file is now the official format.
  • The previous official version 1.9 will be removed from the archive.

Related info.:EMDB header

External links:wwPDB to switch to version 3 of the EMDB data model

-
Aug 12, 2020. Covid-19 info

Covid-19 info

URL: https://pdbj.org/emnavi/covid19.php

New page: Covid-19 featured information page in EM Navigator.

Related info.:Covid-19 info / Mar 5, 2020. Novel coronavirus structure data

+
Mar 5, 2020. Novel coronavirus structure data

Novel coronavirus structure data

Related info.:Yorodumi Speices / Aug 12, 2020. Covid-19 info

External links:COVID-19 featured content - PDBj / Molecule of the Month (242)：Coronavirus Proteases

+
Jan 31, 2019. EMDB accession codes are about to change! (news from PDBe EMDB page)

EMDB accession codes are about to change! (news from PDBe EMDB page)

  • The allocation of 4 digits for EMDB accession codes will soon come to an end. Whilst these codes will remain in use, new EMDB accession codes will include an additional digit and will expand incrementally as the available range of codes is exhausted. The current 4-digit format prefixed with “EMD-” (i.e. EMD-XXXX) will advance to a 5-digit format (i.e. EMD-XXXXX), and so on. It is currently estimated that the 4-digit codes will be depleted around Spring 2019, at which point the 5-digit format will come into force.
  • The EM Navigator/Yorodumi systems omit the EMD- prefix.

Related info.:Q: What is EMD? / ID/Accession-code notation in Yorodumi/EM Navigator

External links:EMDB Accession Codes are Changing Soon! / Contact to PDBj

+
Jul 12, 2017. Major update of PDB

Major update of PDB

  • wwPDB released updated PDB data conforming to the new PDBx/mmCIF dictionary.
  • This is a major update changing the version number from 4 to 5, and with Remediation, in which all the entries are updated.
  • In this update, many items about electron microscopy experimental information are reorganized (e.g. em_software).
  • Now, EM Navigator and Yorodumi are based on the updated data.

External links:wwPDB Remediation / Enriched Model Files Conforming to OneDep Data Standards Now Available in the PDB FTP Archive

-
Yorodumi

Thousand views of thousand structures

  • Yorodumi is a browser for structure data from EMDB, PDB, SASBDB, etc.
  • This page is also the successor to EM Navigator detail page, and also detail information page/front-end page for Omokage search.
  • The word "yorodu" (or yorozu) is an old Japanese word meaning "ten thousand". "mi" (miru) is to see.

Related info.:EMDB / PDB / SASBDB / Comparison of 3 databanks / Yorodumi Search / Aug 31, 2016. New EM Navigator & Yorodumi / Yorodumi Papers / Jmol/JSmol / Function and homology information / Changes in new EM Navigator and Yorodumi

Read more