[English] 日本語
Yorodumi
- PDB-7ewh: Crystal structure of human PHGDH in complex with Homoharringtonine -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7ewh
TitleCrystal structure of human PHGDH in complex with Homoharringtonine
ComponentsD-3-phosphoglycerate dehydrogenase
KeywordsOXIDOREDUCTASE / inhibitor
Function / homology
Function and homology information


gamma-aminobutyric acid metabolic process / threonine metabolic process / 2-oxoglutarate reductase / glial cell development / phosphoglycerate dehydrogenase / phosphoglycerate dehydrogenase activity / taurine metabolic process / Serine biosynthesis / glycine metabolic process / malate dehydrogenase ...gamma-aminobutyric acid metabolic process / threonine metabolic process / 2-oxoglutarate reductase / glial cell development / phosphoglycerate dehydrogenase / phosphoglycerate dehydrogenase activity / taurine metabolic process / Serine biosynthesis / glycine metabolic process / malate dehydrogenase / L-serine biosynthetic process / L-malate dehydrogenase activity / G1 to G0 transition / neural tube development / spinal cord development / glutamine metabolic process / brain development / neuron projection development / NAD binding / regulation of gene expression / electron transfer activity / extracellular exosome / cytosol
Similarity search - Function
D-3-phosphoglycerate dehydrogenase / D-3-phosphoglycerate dehydrogenase, ASB domain / D-3-phosphoglycerate dehydrogenase intervening domain / Allosteric substrate binding domain superfamily / D-isomer specific 2-hydroxyacid dehydrogenases signature 2. / D-isomer specific 2-hydroxyacid dehydrogenases NAD-binding signature. / D-isomer specific 2-hydroxyacid dehydrogenase, NAD-binding domain conserved site 1 / D-isomer specific 2-hydroxyacid dehydrogenases signature 3. / D-isomer specific 2-hydroxyacid dehydrogenase, NAD-binding domain conserved site / D-isomer specific 2-hydroxyacid dehydrogenase, catalytic domain ...D-3-phosphoglycerate dehydrogenase / D-3-phosphoglycerate dehydrogenase, ASB domain / D-3-phosphoglycerate dehydrogenase intervening domain / Allosteric substrate binding domain superfamily / D-isomer specific 2-hydroxyacid dehydrogenases signature 2. / D-isomer specific 2-hydroxyacid dehydrogenases NAD-binding signature. / D-isomer specific 2-hydroxyacid dehydrogenase, NAD-binding domain conserved site 1 / D-isomer specific 2-hydroxyacid dehydrogenases signature 3. / D-isomer specific 2-hydroxyacid dehydrogenase, NAD-binding domain conserved site / D-isomer specific 2-hydroxyacid dehydrogenase, catalytic domain / D-isomer specific 2-hydroxyacid dehydrogenase, catalytic domain / D-isomer specific 2-hydroxyacid dehydrogenase, NAD-binding domain / D-isomer specific 2-hydroxyacid dehydrogenase, NAD binding domain / NAD(P)-binding domain superfamily
Similarity search - Domain/homology
Chem-HMT / D-3-phosphoglycerate dehydrogenase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.99 Å
AuthorsHsieh, C.H. / Cheng, Y.S. / Lee, Y.S. / Huang, H.C. / Juan, H.F.
Funding support Taiwan, 2items
OrganizationGrant numberCountry
Ministry of Science and Technology (MoST, Taiwan)MOST-109-2320-B-002-017-MY3 Taiwan
Ministry of Science and Technology (MoST, Taiwan)MOST-109-2221-E-002-161-MY3 Taiwan
CitationJournal: Biomed Pharmacother / Year: 2023
Title: Homoharringtonine as a PHGDH inhibitor: Unraveling metabolic dependencies and developing a potent therapeutic strategy for high-risk neuroblastoma.
Authors: Hsieh, C.H. / Huang, C.T. / Cheng, Y.S. / Hsu, C.H. / Hsu, W.M. / Chung, Y.H. / Liu, Y.L. / Yang, T.S. / Chien, C.Y. / Lee, Y.H. / Huang, H.C. / Juan, H.F.
History
DepositionMay 25, 2021Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Dec 7, 2022Provider: repository / Type: Initial release
Revision 1.1Nov 29, 2023Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model / struct_ncs_dom_lim
Item: _struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id ..._struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id / _struct_ncs_dom_lim.beg_label_comp_id / _struct_ncs_dom_lim.beg_label_seq_id / _struct_ncs_dom_lim.end_auth_comp_id / _struct_ncs_dom_lim.end_label_asym_id / _struct_ncs_dom_lim.end_label_comp_id / _struct_ncs_dom_lim.end_label_seq_id
Revision 1.2Dec 20, 2023Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _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.year

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: D-3-phosphoglycerate dehydrogenase
B: D-3-phosphoglycerate dehydrogenase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)66,0004
Polymers64,9092
Non-polymers1,0912
Water43224
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area5040 Å2
ΔGint-26 kcal/mol
Surface area24780 Å2
MethodPISA
Unit cell
Length a, b, c (Å)43.165, 120.639, 59.480
Angle α, β, γ (deg.)90.000, 100.720, 90.000
Int Tables number4
Space group name H-MP1211
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11chain A
21chain B

NCS domain segments:

Component-ID: 1 / Ens-ID: 1 / Beg auth comp-ID: LEU / Beg label comp-ID: LEU / End auth comp-ID: VAL / End label comp-ID: VAL / Auth seq-ID: 5 - 306 / Label seq-ID: 1 - 302

Dom-IDSelection detailsAuth asym-IDLabel asym-ID
1chain AAA
2chain BBB

-
Components

#1: Protein D-3-phosphoglycerate dehydrogenase / 3-PGDH / 2-oxoglutarate reductase / Malate dehydrogenase


Mass: 32454.383 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PHGDH, PGDH3 / Production host: Escherichia coli BL21(DE3) (bacteria) / Strain (production host): BL21(DE3)
References: UniProt: O43175, phosphoglycerate dehydrogenase, 2-oxoglutarate reductase, malate dehydrogenase
#2: Chemical ChemComp-HMT / (3beta)-O~3~-[(2R)-2,6-dihydroxy-2-(2-methoxy-2-oxoethyl)-6-methylheptanoyl]cephalotaxine / Homoharringtonine / Cephalotaxine / [3(R)]-4-methyl 2-hydroxy-2-(4-hydroxy-4-methylpentyl)butanedioate / Omacetaxine mepesuccinate


Mass: 545.621 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C29H39NO9 / Feature type: SUBJECT OF INVESTIGATION / Comment: anticancer, alkaloid*YM
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 24 / 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: 2.35 Å3/Da / Density % sol: 47.62 %
Crystal growTemperature: 298 K / Method: vapor diffusion, sitting drop / Details: 0.1 mM MMT buffer, pH 7.0 with 30% PEG4000

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: NSRRC / Beamline: BL13B1 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 210 / Detector: CCD / Date: Jan 11, 2021
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.99→27.555 Å / Num. obs: 9221 / % possible obs: 75.95 % / Redundancy: 3.7 % / Rmerge(I) obs: 0.136 / Rsym value: 0.159 / Net I/σ(I): 9.002
Reflection shellResolution: 2.99→3.097 Å / Num. unique obs: 481 / CC1/2: 0.899 / Rpim(I) all: 0.281 / Rrim(I) all: 0.529

-
Processing

Software
NameVersionClassification
HKL-2000data scaling
PHENIX1.14_3260refinement
PDB_EXTRACT3.27data extraction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2G76

2g76


Resolution: 2.99→27.555 Å / SU ML: 0.58 / Cross valid method: THROUGHOUT / σ(F): 0 / Phase error: 39.7 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.348 939 10.18 %
Rwork0.2367 8282 -
obs0.2479 9221 76.02 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso max: 145.72 Å2 / Biso mean: 56.0406 Å2 / Biso min: 13.33 Å2
Refinement stepCycle: final / Resolution: 2.99→27.555 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4520 0 78 24 4622
Biso mean--45.52 36.4 -
Num. residues----604
Refine LS restraints NCS
Ens-IDDom-IDAuth asym-IDNumberRefine-IDRmsType
11A1828X-RAY DIFFRACTION15.037TORSIONAL
12B1828X-RAY DIFFRACTION15.037TORSIONAL
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Rfactor Rfree error: 0

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection Rwork% reflection obs (%)
2.99-3.1470.416700.28761340
3.147-3.34390.4521080.284793260
3.3439-3.60150.38261240.2548108770
3.6015-3.9630.38731470.2187128383
3.963-4.53430.33161570.2146137289
4.5343-5.70440.31951620.2517145993
5.7044-27.5550.31171710.2271153697

+
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