[English] 日本語
Yorodumi
- PDB-5wbp: Structure of human Ketohexokinase complexed with hits from fragme... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5wbp
TitleStructure of human Ketohexokinase complexed with hits from fragment screening
ComponentsKetohexokinase
KeywordsTRANSFERASE / Ketohexokinase / Fragment-based drug discovery / SBDD
Function / homology
Function and homology information


Essential fructosuria / ketohexokinase / ketohexokinase activity / fructose binding / Fructose catabolism / regulation of glycogen metabolic process / response to sucrose / response to fructose / fructose metabolic process / response to zinc ion ...Essential fructosuria / ketohexokinase / ketohexokinase activity / fructose binding / Fructose catabolism / regulation of glycogen metabolic process / response to sucrose / response to fructose / fructose metabolic process / response to zinc ion / response to glucose / response to insulin / protein homodimerization activity / extracellular exosome / ATP binding / identical protein binding / cytosol / cytoplasm
Similarity search - Function
Ketohexokinase / : / Carbohydrate kinase PfkB / pfkB family carbohydrate kinase / Ribokinase / Ribokinase-like / UDP-N-acetylmuramoyl-L-alanine:D-glutamate ligase / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
3-(trifluoromethyl)quinoxalin-2(1H)-one / Ketohexokinase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 2.74 Å
AuthorsPandit, J.
CitationJournal: J. Med. Chem. / Year: 2017
Title: Discovery of Fragment-Derived Small Molecules for in Vivo Inhibition of Ketohexokinase (KHK).
Authors: Huard, K. / Ahn, K. / Amor, P. / Beebe, D.A. / Borzilleri, K.A. / Chrunyk, B.A. / Coffey, S.B. / Cong, Y. / Conn, E.L. / Culp, J.S. / Dowling, M.S. / Gorgoglione, M.F. / Gutierrez, J.A. / ...Authors: Huard, K. / Ahn, K. / Amor, P. / Beebe, D.A. / Borzilleri, K.A. / Chrunyk, B.A. / Coffey, S.B. / Cong, Y. / Conn, E.L. / Culp, J.S. / Dowling, M.S. / Gorgoglione, M.F. / Gutierrez, J.A. / Knafels, J.D. / Lachapelle, E.A. / Pandit, J. / Parris, K.D. / Perez, S. / Pfefferkorn, J.A. / Price, D.A. / Raymer, B. / Ross, T.T. / Shavnya, A. / Smith, A.C. / Subashi, T.A. / Tesz, G.J. / Thuma, B.A. / Tu, M. / Weaver, J.D. / Weng, Y. / Withka, J.M. / Xing, G. / Magee, T.V.
History
DepositionJun 29, 2017Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 13, 2017Provider: repository / Type: Initial release
Revision 1.1Oct 11, 2017Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.title / _citation_author.name
Revision 1.2Oct 4, 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: Ketohexokinase
B: Ketohexokinase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)68,9409
Polymers68,1532
Non-polymers7877
Water45025
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4690 Å2
ΔGint-98 kcal/mol
Surface area24620 Å2
MethodPISA
Unit cell
Length a, b, c (Å)82.910, 85.020, 138.780
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein Ketohexokinase / Hepatic fructokinase


Mass: 34076.586 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: KHK / Production host: Escherichia coli (E. coli) / References: UniProt: P50053, ketohexokinase
#2: Chemical ChemComp-A2J / 3-(trifluoromethyl)quinoxalin-2(1H)-one


Mass: 214.144 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C9H5F3N2O
#3: Chemical
ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 5 / Source method: obtained synthetically / Formula: SO4
#4: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C3H8O3
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 25 / 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: 3.59 Å3/Da / Density % sol: 65.72 %
Crystal growTemperature: 293 K / Method: vapor diffusion, sitting drop / pH: 4.5
Details: 17% PEG 8k, 0.1M Na-Citrate, 0.2M Ammonium sulfate, pH 4.5
Temp details: Room temperature

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Oct 2, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.74→138.78 Å / Num. obs: 26032 / % possible obs: 98.6 % / Redundancy: 6.1 % / Biso Wilson estimate: 95.74 Å2 / Rpim(I) all: 0.018 / Rrim(I) all: 0.046 / Rsym value: 0.038 / Net I/av σ(I): 14.2 / Net I/σ(I): 25.5
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsRpim(I) allRrim(I) allRsym value% possible all
2.74-2.894.10.4141.90.2530.5410.41490.5
2.89-3.076.30.2732.80.1280.3270.273100
3.07-3.286.80.15450.0690.1810.154100
3.28-3.546.50.0799.60.0370.0940.079100
3.54-3.886.60.04914.70.0230.0590.049100
3.88-4.346.70.03619.70.0160.0420.036100
4.34-5.016.20.02923.10.0140.0340.029100
5.01-6.136.20.02823.40.0130.0330.028100
6.13-8.686.10.02326.50.0110.0270.023100
8.68-138.785.50.021280.010.0240.02199.7

-
Processing

Software
NameVersionClassification
SCALA3.3.16data scaling
BUSTER2.11.5refinement
PDB_EXTRACT3.22data extraction
XDSdata reduction
BUSTERphasing
RefinementMethod to determine structure: FOURIER SYNTHESIS
Starting model: 3NBV

3nbv


Resolution: 2.74→71.17 Å / Cor.coef. Fo:Fc: 0.9463 / Cor.coef. Fo:Fc free: 0.9313 / SU R Cruickshank DPI: 0.398 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.391 / SU Rfree Blow DPI: 0.26 / SU Rfree Cruickshank DPI: 0.265
RfactorNum. reflection% reflectionSelection details
Rfree0.2285 1322 5.09 %RANDOM
Rwork0.1837 ---
obs0.186 25976 98.24 %-
Displacement parametersBiso max: 174.09 Å2 / Biso mean: 89.38 Å2 / Biso min: 41.46 Å2
Baniso -1Baniso -2Baniso -3
1-18.1095 Å20 Å20 Å2
2---6.8529 Å20 Å2
3----11.2566 Å2
Refine analyzeLuzzati coordinate error obs: 0.379 Å
Refinement stepCycle: final / Resolution: 2.74→71.17 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4547 0 59 25 4631
Biso mean--123.18 74.6 -
Num. residues----597
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d1625SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes120HARMONIC2
X-RAY DIFFRACTIONt_gen_planes708HARMONIC5
X-RAY DIFFRACTIONt_it4693HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion583SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact5097SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d4693HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg6363HARMONIC21.17
X-RAY DIFFRACTIONt_omega_torsion3.02
X-RAY DIFFRACTIONt_other_torsion20.89
LS refinement shellResolution: 2.74→2.85 Å / Rfactor Rfree error: 0 / Total num. of bins used: 13
RfactorNum. reflection% reflection
Rfree0.3222 134 5.44 %
Rwork0.2489 2331 -
all0.2529 2465 -
obs--98.24 %

+
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