[English] 日本語
Yorodumi
- PDB-5ox5: HIF prolyl hydroxylase 2 (PHD2/ EGLN1) in complex with CCT6, a GS... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5ox5
TitleHIF prolyl hydroxylase 2 (PHD2/ EGLN1) in complex with CCT6, a GSK1278863-related compound
ComponentsEgl nine homolog 1
KeywordsOXIDOREDUCTASE / NON-HEME DIOXYGENASE / IRON / 2-OXOGLUTARATE / HYPOXIA-INDUCIBLE FACTOR / HIF / HIF PROLYL HYDROXYLASE DOMAIN 2 / PHD2 / EGLN1 / OXYGENASE / HYPOXIA / DNA-BINDING / METAL-BINDING / TRANSCRIPTION / HELIX-LOOP-HELIX-BETA / DSBH / FACIAL TRIAD / CYTOPLASM / TRANSCRIPTION/EPIGENETIC REGULATION / SIGNALING / DEVELOPMENT / CELL STRUCTURE / BETA-HYDROXYLATION / TRANSCRIPTION ACTIVATOR/INHIBITOR / UBL CONJUGATION / POLYMORPHISM / VITAMIN C / ZINC-FINGER / FAMILIAL ERYTHROCYTOSIS / BREAST CANCER / TRANSCRIPTION COMPLEX
Function / homology
Function and homology information


peptidyl-proline 4-dioxygenase activity / hypoxia-inducible factor-proline dioxygenase activity / hypoxia-inducible factor-proline dioxygenase / negative regulation of hypoxia-inducible factor-1alpha signaling pathway / peptidyl-proline dioxygenase activity / regulation protein catabolic process at postsynapse / intracellular oxygen homeostasis / regulation of modification of postsynaptic structure / labyrinthine layer development / 2-oxoglutarate-dependent dioxygenase activity ...peptidyl-proline 4-dioxygenase activity / hypoxia-inducible factor-proline dioxygenase activity / hypoxia-inducible factor-proline dioxygenase / negative regulation of hypoxia-inducible factor-1alpha signaling pathway / peptidyl-proline dioxygenase activity / regulation protein catabolic process at postsynapse / intracellular oxygen homeostasis / regulation of modification of postsynaptic structure / labyrinthine layer development / 2-oxoglutarate-dependent dioxygenase activity / heart trabecula formation / cardiac muscle tissue morphogenesis / L-ascorbic acid binding / response to nitric oxide / ventricular septum morphogenesis / enzyme inhibitor activity / regulation of angiogenesis / regulation of neuron apoptotic process / ferrous iron binding / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / cellular response to hypoxia / intracellular iron ion homeostasis / response to hypoxia / postsynaptic density / intracellular membrane-bounded organelle / glutamatergic synapse / enzyme binding / positive regulation of transcription by RNA polymerase II / zinc ion binding / nucleus / cytoplasm / cytosol
Similarity search - Function
: / Prolyl 4-hydroxylase alpha subunit, Fe(2+) 2OG dioxygenase domain / 2OG-Fe(II) oxygenase superfamily / Prolyl 4-hydroxylase, alpha subunit / Prolyl 4-hydroxylase alpha subunit homologues. / MYND finger / Zinc finger MYND-type signature. / Zinc finger, MYND-type / Zinc finger MYND-type profile. / q2cbj1_9rhob like domain ...: / Prolyl 4-hydroxylase alpha subunit, Fe(2+) 2OG dioxygenase domain / 2OG-Fe(II) oxygenase superfamily / Prolyl 4-hydroxylase, alpha subunit / Prolyl 4-hydroxylase alpha subunit homologues. / MYND finger / Zinc finger MYND-type signature. / Zinc finger, MYND-type / Zinc finger MYND-type profile. / q2cbj1_9rhob like domain / Oxoglutarate/iron-dependent dioxygenase / Fe(2+) 2-oxoglutarate dioxygenase domain profile. / Jelly Rolls / Sandwich / Mainly Beta
Similarity search - Domain/homology
Chem-B2E / BICARBONATE ION / : / Egl nine homolog 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.251 Å
AuthorsChowdhury, R. / Thinnes, C.C. / Schofield, C.J.
Citation
Journal: Chem Sci / Year: 2017
Title: Molecular and cellular mechanisms of HIF prolyl hydroxylase inhibitors in clinical trials.
Authors: Yeh, T.L. / Leissing, T.M. / Abboud, M.I. / Thinnes, C.C. / Atasoylu, O. / Holt-Martyn, J.P. / Zhang, D. / Tumber, A. / Lippl, K. / Lohans, C.T. / Leung, I.K.H. / Morcrette, H. / Clifton, I. ...Authors: Yeh, T.L. / Leissing, T.M. / Abboud, M.I. / Thinnes, C.C. / Atasoylu, O. / Holt-Martyn, J.P. / Zhang, D. / Tumber, A. / Lippl, K. / Lohans, C.T. / Leung, I.K.H. / Morcrette, H. / Clifton, I.J. / Claridge, T.D.W. / Kawamura, A. / Flashman, E. / Lu, X. / Ratcliffe, P.J. / Chowdhury, R. / Pugh, C.W. / Schofield, C.J.
#1: Journal: ACS Chem. Biol. / Year: 2013
Title: Selective small molecule probes for the hypoxia inducible factor (HIF) prolyl hydroxylases.
Authors: Chowdhury, R. / Candela-Lena, J.I. / Chan, M.C. / Greenald, D.J. / Yeoh, K.K. / Tian, Y.M. / McDonough, M.A. / Tumber, A. / Rose, N.R. / Conejo-Garcia, A. / Demetriades, M. / Mathavan, S. / ...Authors: Chowdhury, R. / Candela-Lena, J.I. / Chan, M.C. / Greenald, D.J. / Yeoh, K.K. / Tian, Y.M. / McDonough, M.A. / Tumber, A. / Rose, N.R. / Conejo-Garcia, A. / Demetriades, M. / Mathavan, S. / Kawamura, A. / Lee, M.K. / van Eeden, F. / Pugh, C.W. / Ratcliffe, P.J. / Schofield, C.J.
#2: Journal: PLoS ONE / Year: 2015
Title: Potent and Selective Triazole-Based Inhibitors of the Hypoxia-Inducible Factor Prolyl-Hydroxylases with Activity in the Murine Brain.
Authors: Chan, M.C. / Atasoylu, O. / Hodson, E. / Tumber, A. / Leung, I.K. / Chowdhury, R. / Gomez-Perez, V. / Demetriades, M. / Rydzik, A.M. / Holt-Martyn, J. / Tian, Y.M. / Bishop, T. / Claridge, T. ...Authors: Chan, M.C. / Atasoylu, O. / Hodson, E. / Tumber, A. / Leung, I.K. / Chowdhury, R. / Gomez-Perez, V. / Demetriades, M. / Rydzik, A.M. / Holt-Martyn, J. / Tian, Y.M. / Bishop, T. / Claridge, T.D. / Kawamura, A. / Pugh, C.W. / Ratcliffe, P.J. / Schofield, C.J.
History
DepositionSep 6, 2017Deposition site: PDBE / Processing site: PDBE
Revision 1.0Oct 18, 2017Provider: repository / Type: Initial release
Revision 1.1Feb 21, 2018Group: Database references / Category: citation / citation_author
Item: _citation.journal_id_ISSN / _citation.journal_volume ..._citation.journal_id_ISSN / _citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_DOI / _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.name
Revision 1.2Jan 17, 2024Group: 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: Egl nine homolog 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)28,4704
Polymers28,0971
Non-polymers3733
Water1,53185
1


  • Idetical with deposited unit
  • defined by software
  • Evidence: gel filtration, MONOMER IN SOLUTION
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area260 Å2
ΔGint-6 kcal/mol
Surface area11070 Å2
MethodPISA
Unit cell
Length a, b, c (Å)110.147, 110.147, 39.368
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number173
Space group name H-MP63

-
Components

#1: Protein Egl nine homolog 1 / Hypoxia-inducible factor prolyl hydroxylase 2 / HPH-2 / Prolyl hydroxylase domain-containing ...Hypoxia-inducible factor prolyl hydroxylase 2 / HPH-2 / Prolyl hydroxylase domain-containing protein 2 / PHD2 / SM-20


Mass: 28096.941 Da / Num. of mol.: 1 / Fragment: CATALYTIC DOMAIN, UNP residues 181-426
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: EGLN1, C1orf12, PNAS-118, PNAS-137 / Plasmid: PET28A(+) / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: Q9GZT9, hypoxia-inducible factor-proline dioxygenase
#2: Chemical ChemComp-MN / MANGANESE (II) ION


Mass: 54.938 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mn
#3: Chemical ChemComp-B2E / (6-hydroxy-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carbonyl)glycine


Mass: 257.200 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C9H11N3O6
#4: Chemical ChemComp-BCT / BICARBONATE ION


Mass: 61.017 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: CHO3
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 85 / 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: 2.77 Å3/Da / Density % sol: 55.68 % / Description: Hexagonal
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.5
Details: 1.5 M sodium citrate tribasic dehydrate pH 6.5, Sitting drop (300 nl), protein-to-well ratio, 1:1.

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I02 / Wavelength: 0.98 Å
DetectorType: DECTRIS PILATUS 6M-F / Detector: PIXEL / Date: May 5, 2015 / Details: MIRRORS
RadiationMonochromator: SI 111 / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.98 Å / Relative weight: 1
ReflectionResolution: 2.25→47.69 Å / Num. obs: 13170 / % possible obs: 100 % / Redundancy: 5.7 % / Biso Wilson estimate: 40 Å2 / CC1/2: 0.994 / Rmerge(I) obs: 0.138 / Rpim(I) all: 0.064 / Net I/σ(I): 12.9
Reflection shellResolution: 2.25→2.33 Å / Redundancy: 5.7 % / Rmerge(I) obs: 0.953 / Mean I/σ(I) obs: 2.1 / Num. unique obs: 1314 / CC1/2: 0.598 / Rpim(I) all: 0.449 / % possible all: 99.9

-
Processing

Software
NameVersionClassification
PHENIX(1.11.1_2575: ???)refinement
HKL-2000706Edata reduction
HKL-2000706Edata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 4BQX

4bqx


Resolution: 2.251→47.69 Å / SU ML: 0.26 / Cross valid method: THROUGHOUT / σ(F): 1.34 / Phase error: 23.82 / Stereochemistry target values: ML
RfactorNum. reflection% reflectionSelection details
Rfree0.2048 645 4.9 %RANDOM
Rwork0.1747 ---
obs0.1761 13160 99.67 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT MODEL / Bsol: 63 Å2 / ksol: 0.43 e/Å3
Displacement parametersBiso mean: 58 Å2
Baniso -1Baniso -2Baniso -3
1-4.95 Å20 Å20 Å2
2--4.95 Å20 Å2
3----9.89 Å2
Refine analyze
FreeObs
Luzzati coordinate error0.29 Å0.25 Å
Luzzati d res low-5 Å
Luzzati sigma a-0.31 Å
Refinement stepCycle: LAST / Resolution: 2.251→47.69 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1676 0 23 85 1784
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0031735
X-RAY DIFFRACTIONf_angle_d0.5532359
X-RAY DIFFRACTIONf_dihedral_angle_d15.4711003
X-RAY DIFFRACTIONf_chiral_restr0.045253
X-RAY DIFFRACTIONf_plane_restr0.003310
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.2515-2.42530.28121000.24722475X-RAY DIFFRACTION98
2.4253-2.66940.24751360.23292472X-RAY DIFFRACTION100
2.6694-3.05560.27411260.20122495X-RAY DIFFRACTION100
3.0556-3.84950.18431370.16162502X-RAY DIFFRACTION100
3.8495-47.70570.17361460.14862571X-RAY DIFFRACTION100
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)
10.14060.06010.06560.1625-0.01280.04910.0430.0336-0.55860.0436-0.0690.17360.5714-0.16670.00470.5165-0.00640.04460.3450.13480.502490.3643-90.185.0384
20.34250.06940.25980.03020.05550.26850.0098-0.80680.27070.5999-0.20210.3883-0.1614-0.5941-0.02190.4320.10570.10410.64960.08630.407380.0893-71.198915.7005
31.51510.0454-1.5850.09480.07951.6798-0.43640.11380.2917-0.1386-0.28790.1436-0.5681-0.1897-0.31660.6387-0.0509-0.1380.35850.02450.581587.425-53.89810.8655
40.13980.0915-0.11410.09950.02440.08080.0395-0.13810.37670.15220.0910.4039-0.1695-0.38770.00010.43280.02870.02330.53360.02210.410691.0163-65.439812.8605
51.36160.14470.90170.88330.38190.60560.0520.00680.01580.1601-0.0379-0.0866-0.0394-0.0031-00.30440.0465-0.00410.30220.08360.299295.2323-76.57296.214
60.30750.4140.32410.9855-0.04080.50220.08170.6543-0.5111-0.30580.00120.14850.1525-0.2826-0.00080.268-0.0099-0.03990.47480.02460.352883.3842-76.8137-5.6339
70.6062-0.02640.97921.09520.21760.1945-0.00230.0735-0.046-0.00260.0225-0.02440.119-0.067-0.0010.28110.0267-0.00420.34370.06780.340594.3367-75.89291.2672
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain 'A' and (resid 188 through 215 )
2X-RAY DIFFRACTION2chain 'A' and (resid 216 through 231 )
3X-RAY DIFFRACTION3chain 'A' and (resid 232 through 251 )
4X-RAY DIFFRACTION4chain 'A' and (resid 252 through 266 )
5X-RAY DIFFRACTION5chain 'A' and (resid 267 through 329 )
6X-RAY DIFFRACTION6chain 'A' and (resid 330 through 353 )
7X-RAY DIFFRACTION7chain 'A' and (resid 354 through 403 )

+
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