[English] 日本語
Yorodumi
- PDB-2px6: Crystal structure of the thioesterase domain of human fatty acid ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2px6
TitleCrystal structure of the thioesterase domain of human fatty acid synthase inhibited by Orlistat
ComponentsThioesterase domain
KeywordsTRANSFERASE / thioesaterse domain / Orlistat / fatty acid synthase / drug complex / tetrahydrolipstatin
Function / homology
Function and homology information


fatty-acid synthase system / (3R)-3-hydroxybutanoyl-[acyl-carrier-protein] hydratase activity / ether lipid biosynthetic process / : / : / (3R)-3-hydroxyoctanoyl-[acyl-carrier-protein] dehydratase activity / neutrophil differentiation / Vitamin B5 (pantothenate) metabolism / enoyl-[acyl-carrier-protein] reductase (NADPH, Re-specific) / glandular epithelial cell development ...fatty-acid synthase system / (3R)-3-hydroxybutanoyl-[acyl-carrier-protein] hydratase activity / ether lipid biosynthetic process / : / : / (3R)-3-hydroxyoctanoyl-[acyl-carrier-protein] dehydratase activity / neutrophil differentiation / Vitamin B5 (pantothenate) metabolism / enoyl-[acyl-carrier-protein] reductase (NADPH, Re-specific) / glandular epithelial cell development / (3R)-3-hydroxydecanoyl-[acyl-carrier-protein] dehydratase activity / : / glycogen granule / establishment of endothelial intestinal barrier / [acyl-carrier-protein] S-acetyltransferase / [acyl-carrier-protein] S-acetyltransferase activity / Fatty acyl-CoA biosynthesis / oleoyl-[acyl-carrier-protein] hydrolase / (3R)-3-hydroxypalmitoyl-[acyl-carrier-protein] dehydratase activity / modulation by host of viral process / ChREBP activates metabolic gene expression / [acyl-carrier-protein] S-malonyltransferase / [acyl-carrier-protein] S-malonyltransferase activity / fatty acid synthase activity / 3-hydroxyacyl-[acyl-carrier-protein] dehydratase / (3R)-3-hydroxymyristoyl-[acyl-carrier-protein] dehydratase activity / 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 / phosphopantetheine binding / monocyte differentiation / 3-oxoacyl-[acyl-carrier-protein] synthase activity / cellular response to interleukin-4 / fatty acid metabolic process / Activation of gene expression by SREBF (SREBP) / osteoblast differentiation / fatty acid biosynthetic process / melanosome / cadherin binding / inflammatory response / Golgi apparatus / RNA binding / extracellular exosome / membrane / plasma membrane / cytosol / cytoplasm
Similarity search - Function
Fatty acid synthase; domain 2 / Protein Yjbj; Chain: A; / : / Fatty acid synthase, pseudo-KR domain / Polyketide and metazoan fatty acid synthase dehydratase (PKS/mFAS DH) domain profile. / Methyltransferase type 12 / Methyltransferase domain / : / Polyketide synthase dehydratase domain / Thioesterase ...Fatty acid synthase; domain 2 / Protein Yjbj; Chain: A; / : / Fatty acid synthase, pseudo-KR domain / Polyketide and metazoan fatty acid synthase dehydratase (PKS/mFAS DH) domain profile. / Methyltransferase type 12 / Methyltransferase domain / : / Polyketide synthase dehydratase domain / Thioesterase / Thioesterase domain / PKS_DH / Polyketide synthase, dehydratase domain / Polyketide synthase, dehydratase domain superfamily / Polyketide synthase, ketoreductase domain / KR domain / Polyketide synthase, C-terminal extension / Ketoacyl-synthetase C-terminal extension / Malonyl-CoA ACP transacylase, ACP-binding / PKS_KR / Acyl transferase domain superfamily / Acyl transferase / Acyl transferase domain / Acyl transferase domain in polyketide synthase (PKS) enzymes. / Alcohol dehydrogenase-like, C-terminal / Acyl transferase/acyl hydrolase/lysophospholipase / Zinc-binding dehydrogenase / Polyketide synthase, enoylreductase domain / Enoylreductase / Ketosynthase family 3 (KS3) domain profile. / Polyketide synthase, phosphopantetheine-binding domain / Phosphopantetheine attachment site / Beta-ketoacyl synthase / Beta-ketoacyl synthase, active site / Ketosynthase family 3 (KS3) active site signature. / 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 / Phosphopantetheine attachment site / Phosphopantetheine attachment site. / Thiolase-like / Phosphopantetheine attachment site / ACP-like superfamily / Carrier protein (CP) domain profile. / Phosphopantetheine binding ACP domain / Alpha/Beta hydrolase fold, catalytic domain / Alpha/Beta hydrolase fold / NAD(P)-binding domain superfamily / S-adenosyl-L-methionine-dependent methyltransferase superfamily / Rossmann fold / Orthogonal Bundle / 3-Layer(aba) Sandwich / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-DH9 / 2,3-DIHYDROXY-1,4-DITHIOBUTANE / Fatty acid synthase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.3 Å
AuthorsPemble IV, C.W. / Johnson, L.C. / Kridel, S.J. / Lowther, W.T.
CitationJournal: Nat.Struct.Mol.Biol. / Year: 2007
Title: Crystal structure of the thioesterase domain of human fatty acid synthase inhibited by Orlistat.
Authors: Pemble, C.W. / Johnson, L.C. / Kridel, S.J. / Lowther, W.T.
History
DepositionMay 14, 2007Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jul 10, 2007Provider: repository / Type: Initial release
Revision 1.1May 1, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Version format compliance
Revision 1.3Aug 30, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_conn / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_conn.pdbx_leaving_atom_flag / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Remark 600HETEROGEN DH9 3000 forms an adduct with SER 2308 and is missing the O2* atom

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Thioesterase domain
B: Thioesterase domain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)70,6445
Polymers69,4622
Non-polymers1,1823
Water95553
1
A: Thioesterase domain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,2452
Polymers34,7311
Non-polymers5141
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
2
B: Thioesterase domain
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,3993
Polymers34,7311
Non-polymers6682
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)41.860, 94.320, 69.720
Angle α, β, γ (deg.)90.00, 95.82, 90.00
Int Tables number4
Space group name H-MP1211
Detailseach chain represents the biological unit

-
Components

#1: Protein Thioesterase domain /


Mass: 34731.203 Da / Num. of mol.: 2 / Fragment: Residues 2200-2511
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: FAS / Plasmid: pET15b / Production host: Escherichia coli (E. coli) / Strain (production host): C41(DE3) / References: UniProt: P49327, fatty-acid synthase system
#2: Chemical ChemComp-DH9 / (2S,3S,5S)-5-[(N-FORMYL-L-LEUCYL)OXY]-2-HEXYL-3-HYDROXYHEXADECANOIC ACID


Mass: 513.750 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C29H55NO6
#3: Chemical ChemComp-DTT / 2,3-DIHYDROXY-1,4-DITHIOBUTANE / 1,4-DITHIOTHREITOL / Dithiothreitol


Mass: 154.251 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C4H10O2S2
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 53 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 1.97 Å3/Da / Density % sol: 37.53 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 4.3
Details: 50mM sodium dihydrogen phosphate, 30-35% PEG 3350, 30mM dithiothreitol, pH 4.3, VAPOR DIFFUSION, HANGING DROP, temperature 298K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: NSLS / Beamline: X12C / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 210 / Detector: CCD
RadiationMonochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.3→39.01 Å / Num. all: 21850 / Num. obs: 21850 / % possible obs: 96 % / Redundancy: 7.1 % / Rmerge(I) obs: 0.06 / Net I/σ(I): 17
Reflection shellResolution: 2.3→2.38 Å / Redundancy: 6.2 % / Rmerge(I) obs: 0.23 / Mean I/σ(I) obs: 6.2 / % possible all: 76.2

-
Processing

Software
NameVersionClassification
REFMAC5.2.0019refinement
CBASSdata collection
d*TREKdata reduction
d*TREKdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 1XKT

1xkt


Resolution: 2.3→39.01 Å / Cor.coef. Fo:Fc: 0.927 / Cor.coef. Fo:Fc free: 0.9 / SU B: 7.796 / SU ML: 0.196 / Cross valid method: THROUGHOUT / ESU R: 0.474 / ESU R Free: 0.282 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS
RfactorNum. reflection% reflectionSelection details
Rfree0.27276 1184 5.1 %RANDOM
Rwork0.225 ---
obs0.22753 21850 96.03 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å / Solvent model: MASK
Displacement parametersBiso mean: 36.96 Å2
Baniso -1Baniso -2Baniso -3
1-0 Å20 Å2-0.01 Å2
2--0 Å20 Å2
3---0 Å2
Refinement stepCycle: LAST / Resolution: 2.3→39.01 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4011 0 79 53 4143
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.010.0224176
X-RAY DIFFRACTIONr_angle_refined_deg1.2731.9845641
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.5575507
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.00823.622185
X-RAY DIFFRACTIONr_dihedral_angle_3_deg17.32215673
X-RAY DIFFRACTIONr_dihedral_angle_4_deg19.8841527
X-RAY DIFFRACTIONr_chiral_restr0.0840.2640
X-RAY DIFFRACTIONr_gen_planes_refined0.0040.023123
X-RAY DIFFRACTIONr_nbd_refined0.2050.21914
X-RAY DIFFRACTIONr_nbtor_refined0.3030.22844
X-RAY DIFFRACTIONr_xyhbond_nbd_refined0.1660.2169
X-RAY DIFFRACTIONr_symmetry_vdw_refined0.2020.263
X-RAY DIFFRACTIONr_symmetry_hbond_refined0.120.25
X-RAY DIFFRACTIONr_mcbond_it0.6611.52646
X-RAY DIFFRACTIONr_mcangle_it1.09324123
X-RAY DIFFRACTIONr_scbond_it1.47531707
X-RAY DIFFRACTIONr_scangle_it2.374.51518
LS refinement shellResolution: 2.3→2.36 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.374 70 -
Rwork0.231 1207 -
obs--73.01 %

+
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