[English] 日本語
Yorodumi
- PDB-5jwp: Crystal structure of human FIH D201E variant in complex with Zn, ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5jwp
TitleCrystal structure of human FIH D201E variant in complex with Zn, alpha-ketoglutarate, and HIF1 alpha peptide.
Components(Hypoxia-inducible factor 1- ...) x 2
KeywordsOXIDOREDUCTASE / Hypoxia sensing / Factor Inhibiting HIF / alpha-ketoglutarate dependent oxygenase / Hypoxia inducible factor / hydroxylase
Function / homology
Function and homology information


epithelial cell differentiation involved in mammary gland alveolus development / neural fold elevation formation / iris morphogenesis / positive regulation of chemokine-mediated signaling pathway / hypoxia-inducible factor-1alpha signaling pathway / elastin metabolic process / glandular epithelial cell maturation / hypoxia-inducible factor-asparagine dioxygenase / : / regulation of transforming growth factor beta2 production ...epithelial cell differentiation involved in mammary gland alveolus development / neural fold elevation formation / iris morphogenesis / positive regulation of chemokine-mediated signaling pathway / hypoxia-inducible factor-1alpha signaling pathway / elastin metabolic process / glandular epithelial cell maturation / hypoxia-inducible factor-asparagine dioxygenase / : / regulation of transforming growth factor beta2 production / [protein]-asparagine 3-dioxygenase activity / connective tissue replacement involved in inflammatory response wound healing / peptidyl-histidine dioxygenase activity / cardiac ventricle morphogenesis / negative regulation of mesenchymal cell apoptotic process / hemoglobin biosynthetic process / peptidyl-aspartic acid 3-dioxygenase activity / positive regulation of hormone biosynthetic process / mesenchymal cell apoptotic process / positive regulation of mitophagy / Cellular response to hypoxia / retina vasculature development in camera-type eye / intestinal epithelial cell maturation / negative regulation of growth / regulation of protein neddylation / collagen metabolic process / PTK6 Expression / intracellular oxygen homeostasis / negative regulation of bone mineralization / carboxylic acid binding / B-1 B cell homeostasis / positive regulation of vasculogenesis / vascular endothelial growth factor production / lactate metabolic process / ankyrin repeat binding / negative regulation of oxidative stress-induced neuron intrinsic apoptotic signaling pathway / transcription regulator activator activity / dopaminergic neuron differentiation / STAT3 nuclear events downstream of ALK signaling / positive regulation of cytokine production involved in inflammatory response / negative regulation of thymocyte apoptotic process / motile cilium / positive regulation of vascular endothelial growth factor receptor signaling pathway / oxygen sensor activity / positive regulation of signaling receptor activity / insulin secretion involved in cellular response to glucose stimulus / response to iron ion / negative regulation of TOR signaling / response to muscle activity / Notch binding / neural crest cell migration / Regulation of gene expression by Hypoxia-inducible Factor / regulation of glycolytic process / embryonic hemopoiesis / DNA-binding transcription repressor activity / regulation of aerobic respiration / DNA-binding transcription activator activity / PTK6 promotes HIF1A stabilization / digestive tract morphogenesis / muscle cell cellular homeostasis / positive regulation of neuroblast proliferation / axonal transport of mitochondrion / positive regulation of epithelial cell migration / negative regulation of Notch signaling pathway / heart looping / bone mineralization / outflow tract morphogenesis / E-box binding / intracellular glucose homeostasis / positive regulation of insulin secretion involved in cellular response to glucose stimulus / TOR signaling / NF-kappaB binding / neuroblast proliferation / positive regulation of vascular endothelial growth factor production / negative regulation of reactive oxygen species metabolic process / embryonic placenta development / epithelial to mesenchymal transition / positive regulation of blood vessel endothelial cell migration / positive regulation of myoblast differentiation / cellular response to interleukin-1 / cis-regulatory region sequence-specific DNA binding / chondrocyte differentiation / positive regulation of chemokine production / axon cytoplasm / positive regulation of endothelial cell proliferation / lactation / positive regulation of glycolytic process / positive regulation of erythrocyte differentiation / negative regulation of miRNA transcription / response to reactive oxygen species / nuclear receptor binding / positive regulation of nitric-oxide synthase activity / RNA polymerase II transcription regulatory region sequence-specific DNA binding / ferrous iron binding / Hsp90 protein binding / euchromatin / visual learning / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / NOTCH1 Intracellular Domain Regulates Transcription / cerebral cortex development
Similarity search - Function
Hypoxia-inducible factor-1 alpha / Clavaminate synthase-like / Hypoxia-inducible factor 1-alpha inhibitor, domain II / HIF-1 alpha, transactivation domain, C-terminal / HIF-1 alpha C terminal transactivation domain / Hypoxia-inducible factor, alpha subunit-like / Hypoxia-inducible factor-1 / Cupin-like domain 8 / Cupin-like domain / PAS fold-3 ...Hypoxia-inducible factor-1 alpha / Clavaminate synthase-like / Hypoxia-inducible factor 1-alpha inhibitor, domain II / HIF-1 alpha, transactivation domain, C-terminal / HIF-1 alpha C terminal transactivation domain / Hypoxia-inducible factor, alpha subunit-like / Hypoxia-inducible factor-1 / Cupin-like domain 8 / Cupin-like domain / PAS fold-3 / PAS fold / PAC motif / Motif C-terminal to PAS motifs (likely to contribute to PAS structural domain) / A domain family that is part of the cupin metalloenzyme superfamily. / Jelly Rolls / JmjC domain / JmjC domain profile. / Helix-loop-helix DNA-binding domain superfamily / helix loop helix domain / Myc-type, basic helix-loop-helix (bHLH) domain / Myc-type, basic helix-loop-helix (bHLH) domain profile. / PAS fold / PAS fold / PAS domain / PAS repeat profile. / PAS domain / RmlC-like jelly roll fold / PAS domain superfamily / Helix Hairpins / Jelly Rolls / Sandwich / Orthogonal Bundle / Mainly Beta / Mainly Alpha
Similarity search - Domain/homology
2-OXOGLUTARIC ACID / Hypoxia-inducible factor 1-alpha / Hypoxia-inducible factor 1-alpha inhibitor
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.1 Å
Model detailsmature form of protein
AuthorsTaabazuing, C.Y. / Garman, S.C. / Eron, S. / Knapp, M.J.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)T32-GM008515 United States
CitationJournal: J.Inorg.Biochem. / Year: 2016
Title: The facial triad in the alpha-ketoglutarate dependent oxygenase FIH: A role for sterics in linking substrate binding to O2 activation.
Authors: Hangasky, J.A. / Taabazuing, C.Y. / Martin, C.B. / Eron, S.J. / Knapp, M.J.
History
DepositionMay 12, 2016Deposition site: RCSB / Processing site: RCSB
Revision 1.0Nov 23, 2016Provider: repository / Type: Initial release
Revision 2.0Sep 27, 2017Group: Author supporting evidence / Database references / Polymer sequence
Category: citation / entity_poly / pdbx_audit_support
Item: _citation.journal_id_CSD / _entity_poly.pdbx_target_identifier / _pdbx_audit_support.funding_organization
Revision 2.1Dec 25, 2019Group: Author supporting evidence / Category: pdbx_audit_support / Item: _pdbx_audit_support.funding_organization
Revision 2.2Sep 27, 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: Hypoxia-inducible factor 1-alpha inhibitor
B: Hypoxia-inducible factor 1-alpha
hetero molecules


Theoretical massNumber of molelcules
Total (without water)43,3329
Polymers42,6442
Non-polymers6887
Water3,135174
1
A: Hypoxia-inducible factor 1-alpha inhibitor
B: Hypoxia-inducible factor 1-alpha
hetero molecules

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


Theoretical massNumber of molelcules
Total (without water)86,66318
Polymers85,2874
Non-polymers1,37614
Water724
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation7_465y-1,x+1,-z1
Buried area10070 Å2
ΔGint-240 kcal/mol
Surface area31350 Å2
MethodPISA
Unit cell
Length a, b, c (Å)86.220, 86.220, 149.903
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number92
Space group name H-MP41212

-
Components

-
Hypoxia-inducible factor 1- ... , 2 types, 2 molecules AB

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


Mass: 40624.578 Da / Num. of mol.: 1 / Mutation: D201E
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HIF1AN, FIH1 / Plasmid: pET28a / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3)
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
#2: Protein/peptide Hypoxia-inducible factor 1-alpha / HIF1-alpha / ARNT-interacting protein / Basic-helix-loop-helix-PAS protein MOP1 / Class E basic ...HIF1-alpha / ARNT-interacting protein / Basic-helix-loop-helix-PAS protein MOP1 / Class E basic helix-loop-helix protein 78 / bHLHe78 / Member of PAS protein 1 / PAS domain-containing protein 8


Mass: 2019.124 Da / Num. of mol.: 1 / Fragment: UNP residues 11-29 / Source method: obtained synthetically / Source: (synth.) Homo sapiens (human) / References: UniProt: Q16665

-
Non-polymers , 5 types, 181 molecules

#3: Chemical ChemComp-AKG / 2-OXOGLUTARIC ACID / Α-Ketoglutaric acid


Mass: 146.098 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C5H6O5
#4: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL / Glycerol


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#5: Chemical ChemComp-ZN / ZINC ION


Mass: 65.409 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Zn
#6: Chemical
ChemComp-SO4 / SULFATE ION / Sulfate


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


Mass: 18.015 Da / Num. of mol.: 174 / 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: 3.27 Å3/Da / Density % sol: 62.34 % / Mosaicity: 0.663 °
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 7.5 / Details: 0.1M Hepes, 1.6mM ammonium sulfate, 3% PEG 400

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: NSLS / Beamline: X6A / Wavelength: 1.08 Å
DetectorType: ADSC QUANTUM 270 / Detector: CCD / Date: Oct 3, 2013 / Details: FOCUSING MIRRORS
RadiationMonochromator: SI(111) CHANNEL CUT / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.08 Å / Relative weight: 1
ReflectionResolution: 2.1→50 Å / Num. obs: 33713 / % possible obs: 99.5 % / Redundancy: 5.2 % / Rmerge(I) obs: 0.07 / Net I/av σ(I): 24.754 / Net I/σ(I): 11.6
Reflection shell
Resolution (Å)Redundancy (%)Diffraction-ID% possible allRmerge(I) obs
2.1-2.145.3199.8
2.14-2.185.31100
2.18-2.225.3199.90.769
2.22-2.265.311000.634
2.26-2.315.3199.90.582
2.31-2.375.3199.90.52
2.37-2.425.311000.405
2.42-2.495.311000.336
2.49-2.565.3199.90.296
2.56-2.655.3199.90.251
2.65-2.745.3199.90.202
2.74-2.855.3199.90.155
2.85-2.985.3199.90.121
2.98-3.145.4199.80.092
3.14-3.335.3199.90.071
3.33-3.595.3199.80.055
3.59-3.955.2199.60.049
3.95-4.524.9198.20.044
4.52-5.74.9198.20.043
5.7-504.6195.30.043

-
Processing

Software
NameVersionClassification
HKL-2000data collection
HKL-2000data scaling
REFMAC5.7.0032refinement
PDB_EXTRACT3.2data extraction
HKL-2000data reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 1H2L

1h2l


Resolution: 2.1→34.37 Å / Cor.coef. Fo:Fc: 0.969 / Cor.coef. Fo:Fc free: 0.956 / SU B: 7.981 / SU ML: 0.108 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.168 / ESU R Free: 0.154
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.2087 1763 5.9 %RANDOM
Rwork0.1704 ---
obs0.1727 28327 89.13 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso max: 138.4 Å2 / Biso mean: 52.566 Å2 / Biso min: 28.08 Å2
Baniso -1Baniso -2Baniso -3
1--0.05 Å2-0 Å2-0 Å2
2---0.05 Å2-0 Å2
3---0.1 Å2
Refinement stepCycle: final / Resolution: 2.1→34.37 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2903 0 37 174 3114
Biso mean--71.73 53.05 -
Num. residues----355
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0190.0193016
X-RAY DIFFRACTIONr_bond_other_d0.0010.022756
X-RAY DIFFRACTIONr_angle_refined_deg1.9041.9584095
X-RAY DIFFRACTIONr_angle_other_deg0.91536349
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.7855353
X-RAY DIFFRACTIONr_dihedral_angle_2_deg39.5424.658161
X-RAY DIFFRACTIONr_dihedral_angle_3_deg16.44215491
X-RAY DIFFRACTIONr_dihedral_angle_4_deg17.8851517
X-RAY DIFFRACTIONr_chiral_restr0.1180.2416
X-RAY DIFFRACTIONr_gen_planes_refined0.010.0213456
X-RAY DIFFRACTIONr_gen_planes_other0.0010.02729
X-RAY DIFFRACTIONr_mcbond_it3.8314.1781418
X-RAY DIFFRACTIONr_mcbond_other3.8314.1761417
X-RAY DIFFRACTIONr_mcangle_it5.0546.2421769
LS refinement shellResolution: 2.1→2.154 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.288 119 -
Rwork0.263 1846 -
all-1965 -
obs--80.9 %
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)
10.8384-0.3159-0.5050.28880.13140.3677-0.0111-0.0183-0.07280.05380.00730.0167-0.00410.07120.00380.01580.0097-0.00920.1107-0.05320.052-27.897821.3803-9.5337
24.4574-2.85230.78292.3921-1.11481.2854-0.0488-0.25330.52730.15070.1771-0.4138-0.18380.1935-0.12830.0312-0.01570.00430.157-0.19360.2548-28.785235.6834-4.0457
Refinement TLS group
IDRefine-IDRefine TLS-IDAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1A8 - 349
2X-RAY DIFFRACTION1A401 - 402
3X-RAY DIFFRACTION2B794 - 806

+
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