[English] 日本語
Yorodumi
- PDB-8k72: Factor-inhibiting hypoxia-inducible factor in complex with Zn(II)... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 8k72
TitleFactor-inhibiting hypoxia-inducible factor in complex with Zn(II) and 2-(3-hydroxy-2-((3-(phenylsulfonamido)propanoyl)imino)-2,3-dihydrothiazol-4-yl)acetic acid
ComponentsHypoxia-inducible factor 1-alpha inhibitor
KeywordsOXIDOREDUCTASE / factor-inhibiting hypoxia-inducible factor / FIH / 2OG dependent dioxygenase
Function / homology
Function and homology information


hypoxia-inducible factor-asparagine dioxygenase / : / [protein]-asparagine 3-dioxygenase activity / peptidyl-histidine dioxygenase activity / peptidyl-aspartic acid 3-dioxygenase activity / regulation of vascular endothelial growth factor receptor signaling pathway / Cellular response to hypoxia / positive regulation of vasculogenesis / carboxylic acid binding / ankyrin repeat binding ...hypoxia-inducible factor-asparagine dioxygenase / : / [protein]-asparagine 3-dioxygenase activity / peptidyl-histidine dioxygenase activity / peptidyl-aspartic acid 3-dioxygenase activity / regulation of vascular endothelial growth factor receptor signaling pathway / Cellular response to hypoxia / positive regulation of vasculogenesis / carboxylic acid binding / ankyrin repeat binding / Notch binding / oxygen sensor activity / negative regulation of Notch signaling pathway / NF-kappaB binding / positive regulation of myoblast differentiation / ferrous iron binding / transcription corepressor activity / RNA polymerase II-specific DNA-binding transcription factor binding / perinuclear region of cytoplasm / negative regulation of transcription by RNA polymerase II / protein homodimerization activity / zinc ion binding / nucleoplasm / cytosol / cytoplasm
Similarity search - Function
Hypoxia-inducible factor 1-alpha inhibitor, domain II / Cupin-like domain 8 / Cupin-like domain / A domain family that is part of the cupin metalloenzyme superfamily. / JmjC domain / JmjC domain profile. / RmlC-like jelly roll fold
Similarity search - Domain/homology
Chem-VJF / Hypoxia-inducible factor 1-alpha inhibitor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.45 Å
AuthorsNakashima, Y. / Corner, T.P. / Teo, R.Z.R. / Brewitz, L. / Schofield, C.J.
Funding support United Kingdom, 2items
OrganizationGrant numberCountry
Biotechnology and Biological Sciences Research Council (BBSRC)BB/J003018/1 United Kingdom
Biotechnology and Biological Sciences Research Council (BBSRC)BB/R000344/1 United Kingdom
CitationJournal: Chem Sci / Year: 2023
Title: Structure-guided optimisation of N -hydroxythiazole-derived inhibitors of factor inhibiting hypoxia-inducible factor-alpha.
Authors: Corner, T.P. / Teo, R.Z.R. / Wu, Y. / Salah, E. / Nakashima, Y. / Fiorini, G. / Tumber, A. / Brasnett, A. / Holt-Martyn, J.P. / Figg Jr., W.D. / Zhang, X. / Brewitz, L. / Schofield, C.J.
History
DepositionJul 26, 2023Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Dec 13, 2023Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Hypoxia-inducible factor 1-alpha inhibitor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)42,01616
Polymers40,3281
Non-polymers1,68815
Water1,22568
1
A: Hypoxia-inducible factor 1-alpha inhibitor
hetero molecules

A: Hypoxia-inducible factor 1-alpha inhibitor
hetero molecules


Theoretical massNumber of molelcules
Total (without water)84,03232
Polymers80,6572
Non-polymers3,37530
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation7_645y+1,x-1,-z1
Buried area7410 Å2
ΔGint-258 kcal/mol
Surface area31350 Å2
MethodPISA
Unit cell
Length a, b, c (Å)86.610, 86.610, 145.050
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number92
Space group name H-MP41212
Space group name HallP4abw2nw
Symmetry operation#1: x,y,z
#2: -y+1/2,x+1/2,z+1/4
#3: y+1/2,-x+1/2,z+3/4
#4: x+1/2,-y+1/2,-z+3/4
#5: -x+1/2,y+1/2,-z+1/4
#6: -x,-y,z+1/2
#7: y,x,-z
#8: -y,-x,-z+1/2

-
Components

-
Protein , 1 types, 1 molecules A

#1: Protein Hypoxia-inducible factor 1-alpha inhibitor / Factor inhibiting HIF-1 / FIH-1 / Hypoxia-inducible factor asparagine hydroxylase


Mass: 40328.281 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HIF1AN, FIH1 / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: Q9NWT6, hypoxia-inducible factor-asparagine dioxygenase, Oxidoreductases; Acting on paired donors, with incorporation or reduction of molecular oxygen; With 2-oxoglutarate as one ...References: UniProt: Q9NWT6, hypoxia-inducible factor-asparagine dioxygenase, Oxidoreductases; Acting on paired donors, with incorporation or reduction of molecular oxygen; With 2-oxoglutarate as one donor, and incorporation of one atom of oxygen into each donor

-
Non-polymers , 5 types, 83 molecules

#2: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 10 / Source method: obtained synthetically / Formula: SO4
#3: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C3H8O3
#4: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#5: Chemical ChemComp-VJF / 2-[(2~{Z})-3-oxidanyl-2-[3-(phenylsulfonylamino)propanoylimino]-1,3-thiazol-4-yl]ethanoic acid


Mass: 385.415 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C14H15N3O6S2 / Feature type: SUBJECT OF INVESTIGATION
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 68 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 3.37 Å3/Da / Density % sol: 63.53 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 7.5
Details: 0.27 mM FIH, 0.5 mM zinc acetate, 2 mM TC167, 0.1 M HEPES, pH 7.5, 6%w/v PEG400, 1.6 M ammonium sulfate

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I03 / Wavelength: 0.97625 Å
DetectorType: DECTRIS EIGER2 XE 16M / Detector: PIXEL / Date: Nov 20, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.97625 Å / Relative weight: 1
ReflectionResolution: 2.45→72.53 Å / Num. obs: 21056 / % possible obs: 100 % / Redundancy: 26.5 % / Biso Wilson estimate: 72.14 Å2 / CC1/2: 1 / Rmerge(I) obs: 0.168 / Net I/σ(I): 15.1
Reflection shellResolution: 2.45→2.49 Å / Redundancy: 25.6 % / Rmerge(I) obs: 5.078 / Mean I/σ(I) obs: 0.6 / Num. unique obs: 1039 / CC1/2: 0.533 / % possible all: 99.9

-
Processing

Software
NameVersionClassification
PHENIX1.17.1_3660refinement
xia2data reduction
xia2data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4B7K

4b7k


Resolution: 2.45→61.24 Å / SU ML: 0.372 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 30.2521
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2386 1043 4.97 %
Rwork0.2 19936 -
obs0.2018 20979 99.92 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 92.83 Å2
Refinement stepCycle: LAST / Resolution: 2.45→61.24 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2798 0 43 68 2909
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00262943
X-RAY DIFFRACTIONf_angle_d0.5644008
X-RAY DIFFRACTIONf_chiral_restr0.043392
X-RAY DIFFRACTIONf_plane_restr0.0034523
X-RAY DIFFRACTIONf_dihedral_angle_d17.96521071
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.45-2.580.38591550.36232765X-RAY DIFFRACTION99.83
2.58-2.740.32821520.33712784X-RAY DIFFRACTION99.9
2.74-2.950.35831430.29042800X-RAY DIFFRACTION99.93
2.95-3.250.30661520.25722803X-RAY DIFFRACTION99.86
3.25-3.720.24841350.21492866X-RAY DIFFRACTION100
3.72-4.690.21071430.16252871X-RAY DIFFRACTION100
4.69-61.240.20071630.16863047X-RAY DIFFRACTION99.91
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
10.976662484135-0.711971495296-0.4890937123370.4996459568560.3987481548970.316427857631-0.216873662953-0.325341896743-0.2238146559660.635450968821-0.3774662675540.8472336951810.443587441773-0.6551131086230.5568306064631.074315785480.03758467610360.2240470196710.824375963265-0.07190984007471.161608579310.8783008028-29.111345829422.3127324014
22.644542206320.8262006244730.5775549204834.113402690470.8029940025143.185860803260.08106755561490.3427062254780.4970044196210.132106858686-0.1394525847420.615591481-0.420975389959-0.08790878883980.0311180955140.7986699237610.1281601042780.1799857712850.5950401465440.02419630701940.80782290223219.4026933495-16.086453392314.0790892484
33.259690127940.574116444246-0.2422633445970.10826227237-0.03942327188250.0149066092291-0.4136762378871.265200787160.440092056448-0.3577864946140.238225101816-0.09155469707020.151446087806-0.5728583272720.2438730178211.191684196580.008192772992140.1213032726050.9930952506430.08902973754931.1128143854420.6245464319-31.5007114507-7.73135108064
41.038084794541.08480005924-0.8591965813644.10303482910.3846236722212.91591307614-0.1928177010420.773161744011.03317848018-0.862297361948-0.009583231295270.866081764663-0.597748149736-0.6604883247190.1974266715351.450830665950.368216278099-0.1718380904951.076541988470.1587106514211.074597425557.63558852362-14.8731524805-4.45965044731
50.993677160499-0.654051576129-0.6465902499843.662700465012.08744520962.774684349720.05880784296290.05484557762720.156918067506-0.0405464591960.07925386494190.22517461577-0.147131618781-0.0738835327913-0.1337137613460.7412010951160.04641749574950.1136357592390.5602419453950.03405075007030.74620496681821.5343119855-26.57967511659.74496443802
63.6535122147-1.47050480573-1.271409603156.896167745420.2949391526862.53527009915-0.0876717611591-0.06149580299120.697483963091-0.2628556209640.270991224143-0.408437088716-0.06252630404770.256116784722-0.1989749066020.628235094786-0.01927550904470.02300031310560.7710145634250.001046812200070.75761698066739.9567746081-41.32410076222.60224997821
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 12 through 49 )
2X-RAY DIFFRACTION2chain 'A' and (resid 50 through 95 )
3X-RAY DIFFRACTION3chain 'A' and (resid 96 through 119 )
4X-RAY DIFFRACTION4chain 'A' and (resid 120 through 138 )
5X-RAY DIFFRACTION5chain 'A' and (resid 139 through 297 )
6X-RAY DIFFRACTION6chain 'A' and (resid 298 through 349 )

+
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