[English] 日本語
Yorodumi
- PDB-5ajw: Human PFKFB3 in complex with an indole inhibitor 2 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5ajw
TitleHuman PFKFB3 in complex with an indole inhibitor 2
Components6-PHOSPHOFRUCTO-2-KINASE/FRUCTOSE-2,6-BISPHOSPHATASE 3
KeywordsTRANSFERASE
Function / homology
Function and homology information


6-phosphofructo-2-kinase / 6-phosphofructo-2-kinase activity / fructose 2,6-bisphosphate metabolic process / fructose-2,6-bisphosphate 2-phosphatase / fructose-2,6-bisphosphate 2-phosphatase activity / Regulation of glycolysis by fructose 2,6-bisphosphate metabolism / fructose metabolic process / nucleoplasm / ATP binding / cytosol
Similarity search - Function
Fructose-2,6-bisphosphatase / 6-phosphofructo-2-kinase / 6-phosphofructo-2-kinase / Phosphoglycerate/bisphosphoglycerate mutase, active site / Phosphoglycerate mutase family phosphohistidine signature. / Phosphoglycerate mutase family / Phosphoglycerate mutase-like / Histidine phosphatase superfamily, clade-1 / Histidine phosphatase superfamily (branch 1) / Histidine phosphatase superfamily ...Fructose-2,6-bisphosphatase / 6-phosphofructo-2-kinase / 6-phosphofructo-2-kinase / Phosphoglycerate/bisphosphoglycerate mutase, active site / Phosphoglycerate mutase family phosphohistidine signature. / Phosphoglycerate mutase family / Phosphoglycerate mutase-like / Histidine phosphatase superfamily, clade-1 / Histidine phosphatase superfamily (branch 1) / Histidine phosphatase superfamily / P-loop containing nucleotide triphosphate hydrolases / P-loop containing nucleoside triphosphate hydrolase / Rossmann fold / 3-Layer(aba) Sandwich / Alpha Beta
Similarity search - Domain/homology
6-O-phosphono-beta-D-fructofuranose / PHOSPHONIC ACID / PHOSPHATE ION / Chem-S6L / 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3
Similarity search - Component
Biological speciesHOMO SAPIENS (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.5 Å
AuthorsBoyd, S. / Brookfield, J.L. / Critchlow, S.E. / Cumming, I.A. / Curtis, N.J. / Debreczeni, J.E. / Degorce, S.L. / Donald, C. / Evans, N.J. / Groombridge, S. ...Boyd, S. / Brookfield, J.L. / Critchlow, S.E. / Cumming, I.A. / Curtis, N.J. / Debreczeni, J.E. / Degorce, S.L. / Donald, C. / Evans, N.J. / Groombridge, S. / Hopcroft, P. / Jones, N.P. / Kettle, J.G. / Lamont, S. / Lewis, H.J. / MacFaull, P. / McLoughlin, S.B. / Rigoreau, L.J.M. / Smith, J.M. / St-Gallay, S. / Stock, J.K. / Wheatley, E.R. / Winter, J. / Wingfield, J.
CitationJournal: J.Med.Chem. / Year: 2015
Title: Structure-Based Design of Potent and Selective Inhibitors of the Metabolic Kinase Pfkfb3.
Authors: Boyd, S. / Brookfield, J.L. / Critchlow, S.E. / Cumming, I.A. / Curtis, N.J. / Debreczeni, J. / Degorce, S.L. / Donald, C. / Evans, N.J. / Groombridge, S. / Hopcroft, P. / Jones, N.P. / ...Authors: Boyd, S. / Brookfield, J.L. / Critchlow, S.E. / Cumming, I.A. / Curtis, N.J. / Debreczeni, J. / Degorce, S.L. / Donald, C. / Evans, N.J. / Groombridge, S. / Hopcroft, P. / Jones, N.P. / Kettle, J.G. / Lamont, S. / Lewis, H.J. / Macfaull, P. / Mcloughlin, S.B. / Rigoreau, L.J.M. / Smith, J.M. / St-Gallay, S. / Stock, J.K. / Turnbull, A.P. / Wheatley, E.R. / Winter, J. / Wingfield, J.
History
DepositionFeb 27, 2015Deposition site: PDBE / Processing site: PDBE
Revision 1.0Apr 22, 2015Provider: repository / Type: Initial release
Revision 1.1May 13, 2015Group: Database references
Revision 1.2Jul 29, 2020Group: Data collection / Derived calculations ...Data collection / Derived calculations / Other / Structure summary
Category: chem_comp / entity ...chem_comp / entity / pdbx_chem_comp_identifier / pdbx_database_status / pdbx_entity_nonpoly / struct_site / struct_site_gen
Item: _chem_comp.mon_nstd_flag / _chem_comp.name ..._chem_comp.mon_nstd_flag / _chem_comp.name / _chem_comp.type / _entity.pdbx_description / _pdbx_database_status.status_code_sf / _pdbx_entity_nonpoly.name
Description: Carbohydrate remediation / Provider: repository / Type: Remediation

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: 6-PHOSPHOFRUCTO-2-KINASE/FRUCTOSE-2,6-BISPHOSPHATASE 3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)60,5435
Polymers59,6941
Non-polymers8494
Water3,225179
1
A: 6-PHOSPHOFRUCTO-2-KINASE/FRUCTOSE-2,6-BISPHOSPHATASE 3
hetero molecules

A: 6-PHOSPHOFRUCTO-2-KINASE/FRUCTOSE-2,6-BISPHOSPHATASE 3
hetero molecules


Theoretical massNumber of molelcules
Total (without water)121,08510
Polymers119,3882
Non-polymers1,6978
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation12_554x,x-y,-z-1/61
Buried area7690 Å2
ΔGint-43.8 kcal/mol
Surface area37970 Å2
MethodPISA
Unit cell
Length a, b, c (Å)102.530, 102.530, 260.310
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number179
Space group name H-MP6522
Components on special symmetry positions
IDModelComponents
11A-2076-

HOH

-
Components

-
Protein / Sugars , 2 types, 2 molecules A

#1: Protein 6-PHOSPHOFRUCTO-2-KINASE/FRUCTOSE-2,6-BISPHOSPHATASE 3 / 6PF-2-K/FRU-2 / 6-P2ASE 3 / PFK/FBPASE 3 / 6PF-2-K/FRU-2 / 6-P2AS E BRAIN/PLACENTA-TYPE ISOZYME / ...6PF-2-K/FRU-2 / 6-P2ASE 3 / PFK/FBPASE 3 / 6PF-2-K/FRU-2 / 6-P2AS E BRAIN/PLACENTA-TYPE ISOZYME / RENAL CARCINOMA ANTIGEN NY-REN-56 / IPFK-2 / HUMAN PFKFB3


Mass: 59694.137 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) HOMO SAPIENS (human) / Production host: ESCHERICHIA COLI (E. coli) / Strain (production host): BL21
References: UniProt: Q16875, 6-phosphofructo-2-kinase, 6-phosphofructo-2-kinase, fructose-2,6-bisphosphate 2-phosphatase
#4: Sugar ChemComp-F6P / 6-O-phosphono-beta-D-fructofuranose / Fructose 6-phosphate


Type: D-saccharide, beta linking / Mass: 260.136 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Formula: C6H13O9P
IdentifierTypeProgram
b-D-Fruf6PO3IUPAC CARBOHYDRATE SYMBOLPDB-CARE 1.0

-
Non-polymers , 4 types, 182 molecules

#2: Chemical ChemComp-PHS / PHOSPHONIC ACID / Phosphorous acid


Mass: 81.996 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: H3O3P
#3: Chemical ChemComp-PO4 / PHOSPHATE ION / Phosphate


Mass: 94.971 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: PO4
#5: Chemical ChemComp-S6L / 2-amino-N-[4-(2-amino-1-benzyl-3-cyano-indol-5-yl)oxyphenyl]acetamide


Mass: 411.456 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C24H21N5O2
#6: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 179 / 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: 3.31 Å3/Da / Density % sol: 64 % / Description: NONE
Crystal growDetails: 0.2M SODIUM MALONATE, 18W/V% PEG3350 AND 0.1 M PCTP BUFFER PH 7.0

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Type: DIAMOND / Wavelength: 1
DetectorType: DECTRIS PIXEL / Detector: PIXEL
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.5→51.26 Å / Num. obs: 28866 / % possible obs: 99.8 % / Observed criterion σ(I): 2 / Redundancy: 7.1 % / Biso Wilson estimate: 66.93 Å2 / Rmerge(I) obs: 0.07 / Net I/σ(I): 16.9
Reflection shellResolution: 2.5→2.51 Å / Redundancy: 7.3 % / Rmerge(I) obs: 0.49 / Mean I/σ(I) obs: 3.7 / % possible all: 100

-
Processing

Software
NameVersionClassification
BUSTER2.11.6refinement
XDSdata reduction
SCALAdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.5→51.26 Å / Cor.coef. Fo:Fc: 0.9317 / Cor.coef. Fo:Fc free: 0.9177 / SU R Cruickshank DPI: 0.259 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.278 / SU Rfree Blow DPI: 0.206 / SU Rfree Cruickshank DPI: 0.201
RfactorNum. reflection% reflectionSelection details
Rfree0.2234 1496 5.19 %RANDOM
Rwork0.1988 ---
obs0.2001 28821 99.72 %-
Displacement parametersBiso mean: 61 Å2
Baniso -1Baniso -2Baniso -3
1--1.512 Å20 Å20 Å2
2---1.512 Å20 Å2
3---3.024 Å2
Refine analyzeLuzzati coordinate error obs: 0.358 Å
Refinement stepCycle: LAST / Resolution: 2.5→51.26 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3501 0 56 179 3736
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.0093663HARMONIC2
X-RAY DIFFRACTIONt_angle_deg1.064978HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d1280SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes90HARMONIC2
X-RAY DIFFRACTIONt_gen_planes562HARMONIC5
X-RAY DIFFRACTIONt_it3663HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion2.94
X-RAY DIFFRACTIONt_other_torsion18.42
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion470SEMIHARMONIC5
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_contact4258SEMIHARMONIC4
LS refinement shellResolution: 2.5→2.59 Å / Total num. of bins used: 14
RfactorNum. reflection% reflection
Rfree0.2549 148 5.05 %
Rwork0.2119 2780 -
all0.2139 2928 -
obs--99.72 %
Refinement TLS params.Method: refined / Origin x: -30.5485 Å / Origin y: -28.1683 Å / Origin z: -9.1075 Å
111213212223313233
T0.0298 Å2-0.0136 Å20.0295 Å2--0.221 Å20.0119 Å2---0.1608 Å2
L0.9606 °20.0622 °2-0.1817 °2-1.1625 °2-0.0197 °2--1.2986 °2
S0.0181 Å °-0.0314 Å °-0.0964 Å °0.3946 Å °-0.1311 Å °0.0681 Å °0.329 Å °-0.0313 Å °0.113 Å °
Refinement TLS groupSelection details: CHAIN A

+
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