[English] 日本語
Yorodumi
- PDB-4uwd: HIF prolyl hydroxylase 2 (PHD2/ EGLN1) D315E VARIANT in complex w... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4uwd
TitleHIF prolyl hydroxylase 2 (PHD2/ EGLN1) D315E VARIANT in complex with Mn(II) and N-[(1-chloro-4-hydroxyisoquinolin-3-yl)carbonyl]glycine (IOX3/UN9)
ComponentsEGL NINE HOMOLOG 1
KeywordsOXIDOREDUCTASE / NON-HEME / IRON / 2-OXOGLUTARATE / DIOXYGENASE / HYPOXIA-INDUCIBLE FACTOR / HIF / HIF PROLYL HYDROXYLASE DOMAIN 2 / PHD2 / EGLN / OXYGENASE / HYPOXIA / DNA-BINDING / METAL-BINDING / TRANSCRIPTION / HELIX-LOOP-HELIX-BETA / DSBH / FACIAL TRIAD / ASPARAGINYL/ ASPARTYL HYDROXYLASE / TRANSCRIPTION AND EPIGENETIC REGULATION / SIGNALING / DEVELOPMENT / CELL STRUCTURE / ANKYRIN REPEAT DOMAIN / ARD / BETA-HYDROXYLATION / TRANSCRIPTION ACTIVATOR/INHIBITOR / PHOSPHORYLATION / S-NITROSYLATION
Function / homology
Function and homology information


hypoxia-inducible factor-proline dioxygenase activity / hypoxia-inducible factor-proline dioxygenase / peptidyl-proline 4-dioxygenase activity / peptidyl-proline dioxygenase activity / peptidyl-proline hydroxylation to 4-hydroxy-L-proline / negative regulation of cyclic-nucleotide phosphodiesterase activity / regulation protein catabolic process at postsynapse / intracellular oxygen homeostasis / labyrinthine layer development / cardiac muscle tissue morphogenesis ...hypoxia-inducible factor-proline dioxygenase activity / hypoxia-inducible factor-proline dioxygenase / peptidyl-proline 4-dioxygenase activity / peptidyl-proline dioxygenase activity / peptidyl-proline hydroxylation to 4-hydroxy-L-proline / negative regulation of cyclic-nucleotide phosphodiesterase activity / regulation protein catabolic process at postsynapse / intracellular oxygen homeostasis / labyrinthine layer development / cardiac muscle tissue morphogenesis / 2-oxoglutarate-dependent dioxygenase activity / heart trabecula formation / regulation of modification of postsynaptic structure / L-ascorbic acid binding / response to nitric oxide / ventricular septum morphogenesis / regulation of angiogenesis / ferrous iron binding / Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha / negative regulation of DNA-binding transcription factor activity / cellular response to hypoxia / intracellular iron ion homeostasis / postsynaptic density / response to hypoxia / intracellular membrane-bounded organelle / glutamatergic synapse / enzyme binding / positive regulation of transcription by RNA polymerase II / 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. / q2cbj1_9rhob like domain / MYND finger / Zinc finger, MYND-type / Zinc finger MYND-type signature. / Zinc finger MYND-type profile. / Oxoglutarate/iron-dependent dioxygenase ...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. / q2cbj1_9rhob like domain / MYND finger / Zinc finger, MYND-type / Zinc finger MYND-type signature. / Zinc finger MYND-type profile. / Oxoglutarate/iron-dependent dioxygenase / Fe(2+) 2-oxoglutarate dioxygenase domain profile. / Jelly Rolls / Sandwich / Mainly Beta
Similarity search - Domain/homology
: / Chem-UN9 / Egl nine homolog 1
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.721 Å
AuthorsChowdhury, R. / Tarhonskaya, H. / Schofield, C.J.
Citation
Journal: Biochem.J. / Year: 2014
Title: Investigating the Contribution of the Active Site Environment to the Slow Reaction of Hypoxia-Inducible Factor Prolyl Hydroxylase Domain 2 with Oxygen.
Authors: Tarhonskaya, H. / Chowdhury, R. / Leung, I.K.H. / Loik, N.D. / Mccullagh, J.S.O. / Claridge, T.D.W. / Schofield, C.J. / Flashman, E.
#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. / 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. / 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.
History
DepositionAug 11, 2014Deposition site: PDBE / Processing site: PDBE
Revision 1.0Aug 27, 2014Provider: repository / Type: Initial release
Revision 1.1Sep 10, 2014Group: Atomic model / Other
Revision 1.2Oct 22, 2014Group: Database references
Revision 1.3Mar 6, 2019Group: Data collection / Experimental preparation / Other
Category: exptl_crystal_grow / pdbx_database_proc / pdbx_database_status
Item: _exptl_crystal_grow.temp / _pdbx_database_status.recvd_author_approval
Revision 1.4May 8, 2019Group: Data collection / Experimental preparation / Category: exptl_crystal_grow / Item: _exptl_crystal_grow.method
Revision 1.5Jan 10, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Other / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_database_status / pdbx_initial_refinement_model / pdbx_struct_conn_angle / struct_conn / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_database_status.status_code_sf / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_id / _pdbx_struct_conn_angle.ptnr1_label_alt_id / _pdbx_struct_conn_angle.ptnr1_label_asym_id / _pdbx_struct_conn_angle.ptnr1_label_atom_id / _pdbx_struct_conn_angle.ptnr1_label_comp_id / _pdbx_struct_conn_angle.ptnr1_label_seq_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_id / _pdbx_struct_conn_angle.ptnr3_label_alt_id / _pdbx_struct_conn_angle.ptnr3_label_asym_id / _pdbx_struct_conn_angle.ptnr3_label_atom_id / _pdbx_struct_conn_angle.ptnr3_label_comp_id / _pdbx_struct_conn_angle.ptnr3_label_seq_id / _pdbx_struct_conn_angle.value / _struct_conn.pdbx_dist_value / _struct_conn.pdbx_ptnr1_label_alt_id / _struct_conn.pdbx_ptnr2_label_alt_id / _struct_conn.ptnr1_auth_comp_id / _struct_conn.ptnr1_auth_seq_id / _struct_conn.ptnr1_label_asym_id / _struct_conn.ptnr1_label_atom_id / _struct_conn.ptnr1_label_comp_id / _struct_conn.ptnr1_label_seq_id / _struct_conn.ptnr2_auth_comp_id / _struct_conn.ptnr2_auth_seq_id / _struct_conn.ptnr2_label_asym_id / _struct_conn.ptnr2_label_atom_id / _struct_conn.ptnr2_label_comp_id / _struct_conn.ptnr2_label_seq_id / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id

-
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)28,4473
Polymers28,1111
Non-polymers3362
Water2,630146
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)110.520, 110.520, 39.380
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 / HIF-PH2 / HIF -PROLYL HYDROXYLASE 2 / HPH-2 / ...HYPOXIA-INDUCIBLE FACTOR PROLYL HYDROXYLASE 2 / HIF-PH2 / HIF -PROLYL HYDROXYLASE 2 / HPH-2 / PROLYL HYDROXYLASE DOMAIN-CONTAINING PROTEIN 2 / PHD2 / SM-20 / HYPOXIA-INDUCIBLE FACTOR PROLYL HYDROXYLASE 2


Mass: 28110.967 Da / Num. of mol.: 1 / Fragment: CATALYTIC DOMAIN, RESIDUES 181-426 / Mutation: YES
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Plasmid: PET28A / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21(DE3)
References: UniProt: Q9GZT9, procollagen-proline 4-dioxygenase, Oxidoreductases; Acting on paired donors, with incorporation or reduction of molecular oxygen; With 2-oxoglutarate as one donor, and ...References: UniProt: Q9GZT9, procollagen-proline 4-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: Chemical ChemComp-MN / MANGANESE (II) ION


Mass: 54.938 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Mn
#3: Chemical ChemComp-UN9 / N-[(1-CHLORO-4-HYDROXYISOQUINOLIN-3-YL)CARBONYL]GLYCINE


Mass: 280.664 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C12H9ClN2O4
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 146 / 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: 2.6 Å3/Da / Density % sol: 52.3 % / Description: NONE
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 6.5
Details: 0.1M MES PH6.5, 1.7M AMMONIUM SULFATE, 1% DIOXANE, 0.002M MNCL2, SITTING DROP, 293K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I02 / Wavelength: 0.9795
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Mar 17, 2013 / Details: MIRRORS
RadiationMonochromator: SI 111 / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9795 Å / Relative weight: 1
ReflectionResolution: 1.72→47.86 Å / Num. obs: 29428 / % possible obs: 99.9 % / Observed criterion σ(I): 2 / Redundancy: 6.6 % / Biso Wilson estimate: 29.62 Å2 / Rmerge(I) obs: 0.04 / Net I/σ(I): 20.4
Reflection shellResolution: 1.72→1.77 Å / Redundancy: 6.9 % / Rmerge(I) obs: 0.67 / Mean I/σ(I) obs: 3 / % possible all: 99.9

-
Processing

Software
NameVersionClassification
PHENIX(PHENIX.REFINE)refinement
XDSdata reduction
SCALAdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDB ENTRY 4BQY

4bqy


Resolution: 1.721→47.857 Å / SU ML: 0.16 / σ(F): 1.35 / Phase error: 17.05 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.1735 1497 5.1 %
Rwork0.1495 --
obs0.1507 29416 99.94 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 1.721→47.857 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms1684 0 20 146 1850
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0091883
X-RAY DIFFRACTIONf_angle_d1.2162572
X-RAY DIFFRACTIONf_dihedral_angle_d13.787690
X-RAY DIFFRACTIONf_chiral_restr0.048270
X-RAY DIFFRACTIONf_plane_restr0.007344
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.7214-1.7770.27821280.22832524X-RAY DIFFRACTION100
1.777-1.84050.21481230.19262504X-RAY DIFFRACTION100
1.8405-1.91420.20561360.17952526X-RAY DIFFRACTION100
1.9142-2.00130.17621350.17032513X-RAY DIFFRACTION100
2.0013-2.10680.16611600.15422497X-RAY DIFFRACTION100
2.1068-2.23880.15921290.14792524X-RAY DIFFRACTION100
2.2388-2.41170.16741260.14552547X-RAY DIFFRACTION100
2.4117-2.65440.18161330.15512554X-RAY DIFFRACTION100
2.6544-3.03840.17951600.15542521X-RAY DIFFRACTION100
3.0384-3.82780.16651260.14082573X-RAY DIFFRACTION100
3.8278-47.8750.16611410.13882636X-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)
11.6593-0.4622-0.71492.61490.44230.31210.12950.31640.037-0.2562-0.18440.664-0.1168-0.5230.01540.33790.0436-0.10550.40960.03670.388122.22428.1569-0.7477
23.54570.284-0.72823.54830.68171.9407-0.0195-0.0571-0.6772-0.2870.0632-0.22320.2698-0.0104-0.03040.361-0.0313-0.02310.3137-0.00840.340842.21499.0801-4.9451
33.1932-0.017-0.42662.784-0.18944.4891-0.01740.1179-0.2928-0.3345-0.3195-0.53090.47650.4650.25630.34760.01340.01630.32940.04230.354946.297313.489-5.2201
44.2404-2.3121-1.77997.39562.06272.5570.27770.69340.1402-1.1857-0.2980.3602-0.0242-0.6535-0.01280.45560.0371-0.11520.46810.05620.277731.142526.0266-12.0176
51.66190.0596-0.75073.1952-0.10541.42540.0290.00950.21080.112-0.0613-0.1606-0.1291-0.01580.02670.2407-0.0168-0.07560.25090.03480.263138.168525.68541.3951
63.68520.1802-0.63094.12110.32173.99050.0392-0.3513-0.09650.5306-0.08920.63020.2777-0.61140.09490.3029-0.051-0.01670.34880.07150.309230.204615.47359.6131
72.3017-0.2292-0.76952.43020.40751.3922-0.0137-0.06940.01820.1505-0.01830.11110.1094-0.18340.02610.2652-0.0286-0.06730.26380.03330.233733.815920.23894.0822
82.6453-0.0056-2.45650.36380.39182.9196-0.14110.0358-0.6983-0.02350.2763-0.2497-0.10610.4057-0.16690.3607-0.02880.02770.3184-0.01050.521649.462440.3077-2.8747
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 246 )
3X-RAY DIFFRACTION3CHAIN A AND (RESID 247 THROUGH 266 )
4X-RAY DIFFRACTION4CHAIN A AND (RESID 267 THROUGH 282 )
5X-RAY DIFFRACTION5CHAIN A AND (RESID 283 THROUGH 329 )
6X-RAY DIFFRACTION6CHAIN A AND (RESID 330 THROUGH 353 )
7X-RAY DIFFRACTION7CHAIN A AND (RESID 354 THROUGH 391 )
8X-RAY DIFFRACTION8CHAIN A AND (RESID 392 THROUGH 409 )

+
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://pdbjlvh1.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