[English] 日本語
Yorodumi
- PDB-6w0n: Structure of KHK in complex with compound 2 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 6w0n
TitleStructure of KHK in complex with compound 2
ComponentsKetohexokinaseHepatic fructokinase
KeywordsTRANSFERASE / Ketohexokinase
Function / homology
Function and homology information


Essential fructosuria / ketohexokinase / ketohexokinase activity / Fructose catabolism / regulation of glycogen metabolic process / response to sucrose / response to fructose / fructose metabolic process / response to zinc ion / response to glucose ...Essential fructosuria / ketohexokinase / ketohexokinase activity / 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 / extracellular exosome / ATP binding / cytosol / cytoplasm
Similarity search - Function
Ketohexokinase / Carbohydrate kinase PfkB / pfkB family carbohydrate kinase / Ribokinase-like
Similarity search - Domain/homology
CITRIC ACID / Chem-RYS / Ketohexokinase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.41 Å
AuthorsJasti, J.
CitationJournal: J.Med.Chem. / Year: 2020
Title: Discovery of PF-06835919: A Potent Inhibitor of Ketohexokinase (KHK) for the Treatment of Metabolic Disorders Driven by the Overconsumption of Fructose.
Authors: Futatsugi, K. / Smith, A.C. / Tu, M. / Raymer, B. / Ahn, K. / Coffey, S.B. / Dowling, M.S. / Fernando, D.P. / Gutierrez, J.A. / Huard, K. / Jasti, J. / Kalgutkar, A.S. / Knafels, J.D. / ...Authors: Futatsugi, K. / Smith, A.C. / Tu, M. / Raymer, B. / Ahn, K. / Coffey, S.B. / Dowling, M.S. / Fernando, D.P. / Gutierrez, J.A. / Huard, K. / Jasti, J. / Kalgutkar, A.S. / Knafels, J.D. / Pandit, J. / Parris, K.D. / Perez, S. / Pfefferkorn, J.A. / Price, D.A. / Ryder, T. / Shavnya, A. / Stock, I.A. / Tsai, A.S. / Tesz, G.J. / Thuma, B.A. / Weng, Y. / Wisniewska, H.M. / Xing, G. / Zhou, J. / Magee, T.V.
History
DepositionMar 2, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 23, 2020Provider: repository / Type: Initial release
Revision 1.1Sep 30, 2020Group: Database references / Category: citation / citation_author
Item: _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.identifier_ORCID
Revision 1.2Dec 9, 2020Group: Database references / Category: citation / citation_author
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation_author.name
Revision 1.3Oct 11, 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)69,5709
Polymers68,1532
Non-polymers1,4177
Water3,207178
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4790 Å2
ΔGint-64 kcal/mol
Surface area24270 Å2
MethodPISA
Unit cell
Length a, b, c (Å)82.800, 86.170, 137.130
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 / 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-RYS / 6-[(3~{S},4~{R})-3,4-bis(oxidanyl)pyrrolidin-1-yl]-2-[(3~{S})-3-methyl-3-oxidanyl-pyrrolidin-1-yl]-4-(trifluoromethyl)pyridine-3-carbonitrile


Mass: 372.342 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C16H19F3N4O3 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: SO4
#4: Chemical ChemComp-CIT / CITRIC ACID / Citric acid


Mass: 192.124 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C6H8O7
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 178 / 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: 3.59 Å3/Da / Density % sol: 65.73 %
Crystal growTemperature: 295 K / Method: vapor diffusion, sitting drop / pH: 4.5
Details: 17% PEG 8000, 100 mM Na citrate, pH 4.5, and 0.2 M ammonium sulfate

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Oct 19, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.406→137.13 Å / Num. obs: 38668 / % possible obs: 99.5 % / Redundancy: 6 % / CC1/2: 0.999 / Net I/σ(I): 16.5
Reflection shellResolution: 2.406→2.54 Å / Num. unique obs: 5439 / CC1/2: 0.82

-
Processing

Software
NameVersionClassification
BUSTER2.11.7refinement
PDB_EXTRACT3.25data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 5WBM

5wbm


Resolution: 2.41→34.28 Å / Cor.coef. Fo:Fc: 0.95 / Cor.coef. Fo:Fc free: 0.94 / SU R Cruickshank DPI: 0.222 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.226 / SU Rfree Blow DPI: 0.174 / SU Rfree Cruickshank DPI: 0.174
RfactorNum. reflection% reflectionSelection details
Rfree0.204 1936 5.02 %RANDOM
Rwork0.184 ---
obs0.185 38590 99.5 %-
Displacement parametersBiso max: 157.43 Å2 / Biso mean: 63.69 Å2 / Biso min: 32.44 Å2
Baniso -1Baniso -2Baniso -3
1-2.5365 Å20 Å20 Å2
2--2.4148 Å20 Å2
3----4.9514 Å2
Refine analyzeLuzzati coordinate error obs: 0.29 Å
Refinement stepCycle: final / Resolution: 2.41→34.28 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4547 0 103 178 4828
Biso mean--75 59.45 -
Num. residues----597
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d1659SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes839HARMONIC5
X-RAY DIFFRACTIONt_it4741HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion589SEMIHARMONIC5
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_contact5339SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d4741HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg6440HARMONIC21.15
X-RAY DIFFRACTIONt_omega_torsion3.28
X-RAY DIFFRACTIONt_other_torsion18.14
LS refinement shellResolution: 2.41→2.42 Å / Rfactor Rfree error: 0 / Total num. of bins used: 50
RfactorNum. reflection% reflection
Rfree0.2234 51 6.61 %
Rwork0.2316 721 -
all0.231 772 -
obs--85.99 %
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)
11.0561-0.5656-0.19481.82271.12612.50560.16080.24040.3121-0.4072-0.04560.1263-0.7244-0.004-0.11510.0046-0.01520.1132-0.17420.0152-0.05390.037211.687115.8642
21.4450.1035-0.17750.96280.00971.22780.0238-0.2205-0.2819-0.0168-0.0649-0.04810.12990.00580.041-0.13220.04580.0468-0.04650.0817-0.0459-11.419819.385258.0191
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1{ A|* }A3 - 298
2X-RAY DIFFRACTION2{ B|* }B-2 - 298

+
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