[English] 日本語
Yorodumi
- PDB-6vgi: Crystal Structures of FLAP bound to MK-866 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6vgi
TitleCrystal Structures of FLAP bound to MK-866
Components5-lipoxygenase-activating protein
KeywordsMEMBRANE PROTEIN / 5-Lipoxygenase Activating Protein / FLAP / MK-866
Function / homology
Function and homology information


leukotriene production involved in inflammatory response / arachidonate 5-lipoxygenase activity / leukotriene-C4 synthase activity / Synthesis of Lipoxins (LX) / Synthesis of 5-eicosatetraenoic acids / lipoxygenase pathway / Synthesis of Leukotrienes (LT) and Eoxins (EX) / positive regulation of acute inflammatory response / leukotriene biosynthetic process / glutathione peroxidase activity ...leukotriene production involved in inflammatory response / arachidonate 5-lipoxygenase activity / leukotriene-C4 synthase activity / Synthesis of Lipoxins (LX) / Synthesis of 5-eicosatetraenoic acids / lipoxygenase pathway / Synthesis of Leukotrienes (LT) and Eoxins (EX) / positive regulation of acute inflammatory response / leukotriene biosynthetic process / glutathione peroxidase activity / arachidonic acid binding / protein homotrimerization / glutathione transferase activity / enzyme activator activity / cellular response to calcium ion / nuclear envelope / nuclear membrane / protein-containing complex binding / endoplasmic reticulum membrane / enzyme binding / endoplasmic reticulum / membrane / identical protein binding
Similarity search - Function
5-lipoxygenase-activating protein / FLAP/GST2/LTC4S, conserved site / FLAP/GST2/LTC4S family signature. / Membrane-associated, eicosanoid/glutathione metabolism (MAPEG) protein / Membrane associated eicosanoid/glutathione metabolism-like domain superfamily / MAPEG family
Similarity search - Domain/homology
Chem-QY7 / Arachidonate 5-lipoxygenase-activating protein
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.61 Å
AuthorsHo, J.D. / Lee, M.R. / Rauch, C.T. / Aznavour, K. / Park, J.S. / Luz, J.G. / Antonysamy, S. / Condon, B. / Maletic, M. / Zhang, A. ...Ho, J.D. / Lee, M.R. / Rauch, C.T. / Aznavour, K. / Park, J.S. / Luz, J.G. / Antonysamy, S. / Condon, B. / Maletic, M. / Zhang, A. / Hickey, M.J. / Hughes, N.E. / Chandrasekhar, S. / Sloan, A.V. / Gooding, K. / Harvey, A. / Yu, X.P. / Kahl, S.D. / Norman, B.H.
CitationJournal: Biochim Biophys Acta Gen Subj / Year: 2020
Title: Structure-based, multi-targeted drug discovery approach to eicosanoid inhibition: Dual inhibitors of mPGES-1 and 5-lipoxygenase activating protein (FLAP).
Authors: Ho, J.D. / Lee, M.R. / Rauch, C.T. / Aznavour, K. / Park, J.S. / Luz, J.G. / Antonysamy, S. / Condon, B. / Maletic, M. / Zhang, A. / Hickey, M.J. / Hughes, N.E. / Chandrasekhar, S. / Sloan, ...Authors: Ho, J.D. / Lee, M.R. / Rauch, C.T. / Aznavour, K. / Park, J.S. / Luz, J.G. / Antonysamy, S. / Condon, B. / Maletic, M. / Zhang, A. / Hickey, M.J. / Hughes, N.E. / Chandrasekhar, S. / Sloan, A.V. / Gooding, K. / Harvey, A. / Yu, X.P. / Kahl, S.D. / Norman, B.H.
History
DepositionJan 8, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 2, 2020Provider: repository / Type: Initial release
Revision 1.1Dec 9, 2020Group: Database references / Category: citation / citation_author
Item: _citation.journal_id_ISSN / _citation.page_first ..._citation.journal_id_ISSN / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.identifier_ORCID
Revision 1.2Dec 16, 2020Group: Database references / Category: citation / Item: _citation.journal_volume
Revision 1.3Oct 11, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: 5-lipoxygenase-activating protein
B: 5-lipoxygenase-activating protein
C: 5-lipoxygenase-activating protein
D: 5-lipoxygenase-activating protein
E: 5-lipoxygenase-activating protein
F: 5-lipoxygenase-activating protein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)119,27617
Polymers115,9636
Non-polymers3,31311
Water52229
1
A: 5-lipoxygenase-activating protein
E: 5-lipoxygenase-activating protein
F: 5-lipoxygenase-activating protein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)59,6869
Polymers57,9823
Non-polymers1,7046
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area8860 Å2
ΔGint-102 kcal/mol
Surface area23190 Å2
MethodPISA
2
B: 5-lipoxygenase-activating protein
C: 5-lipoxygenase-activating protein
D: 5-lipoxygenase-activating protein
hetero molecules


Theoretical massNumber of molelcules
Total (without water)59,5908
Polymers57,9823
Non-polymers1,6085
Water543
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area8340 Å2
ΔGint-86 kcal/mol
Surface area22730 Å2
MethodPISA
Unit cell
Length a, b, c (Å)214.418, 66.297, 109.430
Angle α, β, γ (deg.)90.000, 101.530, 90.000
Int Tables number5
Space group name H-MC121

-
Components

#1: Protein
5-lipoxygenase-activating protein / / FLAP / MK-886-binding protein


Mass: 19327.193 Da / Num. of mol.: 6
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ALOX5AP, FLAP / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P20292
#2: Chemical
ChemComp-QY7 / 3-[3-(tert-butylsulfanyl)-1-[(4-chlorophenyl)methyl]-5-(propan-2-yl)-1H-indol-2-yl]-2,2-dimethylpropanoic acid


Mass: 472.082 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C27H34ClNO2S / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: SO4
#4: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 29 / 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: 3.29 Å3/Da / Density % sol: 62.57 %
Crystal growTemperature: 298 K / Method: vapor diffusion / pH: 4.6
Details: 28% PEG 550 MME, 200 mM Ammonium Sulfate, 100mM Sodium Acetate pH 4.6, 1 mM MK-886

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 31-ID / Wavelength: 0.9802 Å
DetectorType: RAYONIX MX-225 / Detector: CCD / Date: Sep 18, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9802 Å / Relative weight: 1
ReflectionResolution: 2.61→55.95 Å / Num. obs: 43561 / % possible obs: 100 % / Redundancy: 3.7 % / Rsym value: 0.066 / Net I/σ(I): 12.4
Reflection shellResolution: 2.61→2.75 Å / Num. unique obs: 3145 / Rsym value: 0.42

-
Processing

Software
NameVersionClassification
REFMAC5.5.0109refinement
PDB_EXTRACT3.25data extraction
MOSFLMdata reduction
SCALAdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2Q7M

2q7m


Resolution: 2.61→30 Å / Cor.coef. Fo:Fc: 0.905 / Cor.coef. Fo:Fc free: 0.913 / SU B: 10.852 / SU ML: 0.236 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.474 / ESU R Free: 0.297 / Details: U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2763 2318 5.1 %RANDOM
Rwork0.2585 ---
obs0.2594 43561 100 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.4 Å
Displacement parametersBiso max: 102.46 Å2 / Biso mean: 53.306 Å2 / Biso min: 11.91 Å2
Baniso -1Baniso -2Baniso -3
1--4 Å20 Å20.18 Å2
2--5.42 Å20 Å2
3----1.34 Å2
Refinement stepCycle: final / Resolution: 2.61→30 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6900 0 217 30 7147
Biso mean--60.12 44.27 -
Num. residues----870
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0060.0227296
X-RAY DIFFRACTIONr_angle_refined_deg0.8311.9789949
X-RAY DIFFRACTIONr_dihedral_angle_1_deg3.4935852
X-RAY DIFFRACTIONr_dihedral_angle_2_deg30.13623.139309
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.651151072
X-RAY DIFFRACTIONr_dihedral_angle_4_deg13.2061525
X-RAY DIFFRACTIONr_chiral_restr0.0520.21135
X-RAY DIFFRACTIONr_gen_planes_refined0.0030.025447
LS refinement shellResolution: 2.61→2.677 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.306 175 -
Rwork0.29 3145 -
all-3320 -
obs--100 %

+
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