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

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7mhd
TitleThioesterase Domain of Human Fatty Acid Synthase (FASN-TE) binding a competitive inhibitor SBP-7635
ComponentsFatty acid synthase
KeywordsHydrolase/Inhibitor / THIOESTERASE DOMAIN / FATTY ACID SYNTHASE / 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 / 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
: / 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. / Acyl transferase domain superfamily / Alcohol dehydrogenase-like, C-terminal / 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. / Polyketide synthase, beta-ketoacyl synthase domain / Beta-ketoacyl synthase, N-terminal / Beta-ketoacyl synthase, C-terminal / 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-ZEP / Fatty acid synthase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.03 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 / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Fatty acid synthase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)32,9292
Polymers32,5251
Non-polymers4051
Water1,910106
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)53.886, 61.486, 77.450
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-ZEP / N,N-diethyl-4-{2-[(2-fluorophenyl)methyl]-1,3-thiazol-4-yl}benzene-1-sulfonamide


Mass: 404.521 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C20H21FN2O2S2 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 106 / 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: 1.97 Å3/Da / Density % sol: 37.64 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop
Details: 0.3 ul of 8 mg/ml FASN-TE in 100 mM NaCl, 50 mM BisTris pH 6.0, 10 mM DTT, 0.5 mM of the inhibitor and 1% DMSO were mixed with 0.2 ul of well solution 10% PEG400, 50 mM TRIS-Cl pH 8.5, 1 mM ...Details: 0.3 ul of 8 mg/ml FASN-TE in 100 mM NaCl, 50 mM BisTris pH 6.0, 10 mM DTT, 0.5 mM of the inhibitor and 1% DMSO were mixed with 0.2 ul of well solution 10% PEG400, 50 mM TRIS-Cl pH 8.5, 1 mM DTT, 1 mM Ethylenediaminetetraacetic acid disodium salt (EDTA), 300 mM NaCl.
PH range: pH 6.0-8.5

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRL / Beamline: BL9-2 / Wavelength: 1.0332 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: May 2, 2016
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.0332 Å / Relative weight: 1
ReflectionResolution: 2→35.93 Å / Num. obs: 16885 / % possible obs: 98.2 % / Redundancy: 4.5 % / Biso Wilson estimate: 39.2 Å2 / Rmerge(I) obs: 0.049 / Net I/σ(I): 15.1
Reflection shellResolution: 2.03→2.08 Å / Redundancy: 3.1 % / Rmerge(I) obs: 0.618 / Mean I/σ(I) obs: 2.1 / Num. unique obs: 1031 / % possible all: 82.5

-
Processing

Software
NameVersionClassification
REFMAC5.8.0257refinement
PDB_EXTRACT3.27data extraction
XDSdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3TJM

3tjm


Resolution: 2.03→35.93 Å / Cor.coef. Fo:Fc: 0.962 / Cor.coef. Fo:Fc free: 0.936 / SU B: 6.13 / SU ML: 0.164 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.242 / ESU R Free: 0.197 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2457 824 4.9 %RANDOM
Rwork0.1928 ---
obs0.1956 16028 97.86 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 109.57 Å2 / Biso mean: 42.494 Å2 / Biso min: 23.58 Å2
Baniso -1Baniso -2Baniso -3
1-0.61 Å20 Å20 Å2
2---1.91 Å20 Å2
3---1.31 Å2
Refinement stepCycle: final / Resolution: 2.03→35.93 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2189 0 27 106 2322
Biso mean--59.91 46.3 -
Num. residues----282
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0070.0132321
X-RAY DIFFRACTIONr_bond_other_d0.0010.0172114
X-RAY DIFFRACTIONr_angle_refined_deg1.5261.6583158
X-RAY DIFFRACTIONr_angle_other_deg1.2891.5774909
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.3085291
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.78221.901121
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.4315379
X-RAY DIFFRACTIONr_dihedral_angle_4_deg20.1841516
X-RAY DIFFRACTIONr_chiral_restr0.0720.2298
X-RAY DIFFRACTIONr_gen_planes_refined0.0080.022632
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02492
LS refinement shellResolution: 2.03→2.083 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.305 37 -
Rwork0.283 991 -
all-1028 -
obs--81.33 %

+
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