[English] 日本語
Yorodumi
- PDB-3vry: Crystal structure of HCK complexed with a pyrrolo-pyrimidine inhi... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 3vry
TitleCrystal structure of HCK complexed with a pyrrolo-pyrimidine inhibitor 4-Amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl-cyclopentane
ComponentsTyrosine-protein kinase HCK
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / tyrosine kinase / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


leukocyte degranulation / innate immune response-activating signaling pathway / leukocyte migration involved in immune response / respiratory burst after phagocytosis / regulation of podosome assembly / FLT3 signaling through SRC family kinases / regulation of phagocytosis / regulation of DNA-binding transcription factor activity / Nef and signal transduction / positive regulation of actin filament polymerization ...leukocyte degranulation / innate immune response-activating signaling pathway / leukocyte migration involved in immune response / respiratory burst after phagocytosis / regulation of podosome assembly / FLT3 signaling through SRC family kinases / regulation of phagocytosis / regulation of DNA-binding transcription factor activity / Nef and signal transduction / positive regulation of actin filament polymerization / Fc-gamma receptor signaling pathway involved in phagocytosis / mesoderm development / FCGR activation / type II interferon-mediated signaling pathway / transport vesicle / Signaling by CSF3 (G-CSF) / phosphotyrosine residue binding / FCGR3A-mediated IL10 synthesis / cell surface receptor protein tyrosine kinase signaling pathway / lipopolysaccharide-mediated signaling pathway / peptidyl-tyrosine phosphorylation / integrin-mediated signaling pathway / cell projection / regulation of actin cytoskeleton organization / non-membrane spanning protein tyrosine kinase activity / FCGR3A-mediated phagocytosis / Regulation of signaling by CBL / non-specific protein-tyrosine kinase / negative regulation of inflammatory response to antigenic stimulus / Inactivation of CSF3 (G-CSF) signaling / caveola / cytoplasmic side of plasma membrane / cytokine-mediated signaling pathway / Signaling by CSF1 (M-CSF) in myeloid cells / regulation of cell shape / protein autophosphorylation / regulation of inflammatory response / protein tyrosine kinase activity / cell differentiation / cytoskeleton / lysosome / protein phosphorylation / cell adhesion / defense response to Gram-positive bacterium / intracellular signal transduction / inflammatory response / signaling receptor binding / focal adhesion / intracellular membrane-bounded organelle / positive regulation of cell population proliferation / lipid binding / negative regulation of apoptotic process / Golgi apparatus / ATP binding / nucleus / plasma membrane / cytosol
Similarity search - Function
Tyrosine-protein kinase HCK, SH2 domain / SH2 domain / SHC Adaptor Protein / SH3 Domains / : / SH3 domain / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain ...Tyrosine-protein kinase HCK, SH2 domain / SH2 domain / SHC Adaptor Protein / SH3 Domains / : / SH3 domain / SH2 domain / Src homology 2 (SH2) domain profile. / Src homology 2 domains / SH2 domain / SH3 type barrels. / Src homology 3 domains / SH2 domain superfamily / SH3-like domain superfamily / Src homology 3 (SH3) domain profile. / SH3 domain / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Tyrosine-protein kinase, active site / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Roll / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / 2-Layer Sandwich / Orthogonal Bundle / Mainly Beta / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-B43 / Tyrosine-protein kinase HCK
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.481 Å
AuthorsKuratani, M. / Tomabechi, Y. / Niwa, H. / Handa, N. / Yokoyama, S.
CitationJournal: Sci Transl Med / Year: 2013
Title: A Pyrrolo-Pyrimidine Derivative Targets Human Primary AML Stem Cells in Vivo
Authors: Saito, Y. / Yuki, H. / Kuratani, M. / Hashizume, Y. / Takagi, S. / Honma, T. / Tanaka, A. / Shirouzu, M. / Mikuni, J. / Handa, N. / Ogahara, I. / Sone, A. / Najima, Y. / Tomabechi, Y. / ...Authors: Saito, Y. / Yuki, H. / Kuratani, M. / Hashizume, Y. / Takagi, S. / Honma, T. / Tanaka, A. / Shirouzu, M. / Mikuni, J. / Handa, N. / Ogahara, I. / Sone, A. / Najima, Y. / Tomabechi, Y. / Wakiyama, M. / Uchida, N. / Tomizawa-Murasawa, M. / Kaneko, A. / Tanaka, S. / Suzuki, N. / Kajita, H. / Aoki, Y. / Ohara, O. / Shultz, L.D. / Fukami, T. / Goto, T. / Taniguchi, S. / Yokoyama, S. / Ishikawa, F.
History
DepositionApr 21, 2012Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0May 1, 2013Provider: repository / Type: Initial release
Revision 1.1Nov 8, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / pdbx_struct_conn_angle / struct_conn / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_conn_angle.ptnr1_auth_asym_id / _pdbx_struct_conn_angle.ptnr1_auth_comp_id / _pdbx_struct_conn_angle.ptnr1_auth_seq_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_asym_id / _pdbx_struct_conn_angle.ptnr3_auth_comp_id / _pdbx_struct_conn_angle.ptnr3_auth_seq_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_leaving_atom_flag / _struct_conn.ptnr1_auth_asym_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_asym_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_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.2Dec 6, 2023Group: Data collection / Category: chem_comp_atom / chem_comp_bond / Item: _chem_comp_atom.atom_id / _chem_comp_bond.atom_id_2
Revision 1.3Nov 6, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Tyrosine-protein kinase HCK
B: Tyrosine-protein kinase HCK
hetero molecules


Theoretical massNumber of molelcules
Total (without water)104,8928
Polymers104,0002
Non-polymers8926
Water4,270237
1
A: Tyrosine-protein kinase HCK
hetero molecules


Theoretical massNumber of molelcules
Total (without water)52,4464
Polymers52,0001
Non-polymers4463
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Tyrosine-protein kinase HCK
hetero molecules


Theoretical massNumber of molelcules
Total (without water)52,4464
Polymers52,0001
Non-polymers4463
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)48.590, 73.880, 178.470
Angle α, β, γ (deg.)90.00, 95.84, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Tyrosine-protein kinase HCK / Hematopoietic cell kinase / Hemopoietic cell kinase / p59-HCK/p60-HCK / p59Hck / p61Hck


Mass: 52000.227 Da / Num. of mol.: 2 / Fragment: UNP residues 81-526 / Mutation: Q528E, Q529E, Q530I
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: HCK / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P08631, non-specific protein-tyrosine kinase
#2: Chemical ChemComp-B43 / 4-Amino-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-7-yl-cyclopentane / 7-cyclopentyl-5-(4-phenoxyphenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-amine


Mass: 370.447 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C23H22N4O
#3: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Cl
#4: Chemical ChemComp-CA / CALCIUM ION


Mass: 40.078 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: Ca
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 237 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION / Number of used crystals: 1

-
Sample preparation

CrystalDensity Matthews: 3.06 Å3/Da / Density % sol: 59.86 %
Crystal growTemperature: 277 K / Method: vapor diffusion, sitting drop / pH: 8
Details: 21% PEG 6000, 180mM calcium acetate, 18% glycerol, 100mM Tris, pH 8.0, VAPOR DIFFUSION, SITTING DROP, temperature 277K

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: SPring-8 / Beamline: BL41XU / Wavelength: 1 Å
DetectorType: RAYONIX MX225HE / Detector: CCD / Date: Apr 25, 2011
RadiationMonochromator: Si 511 / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.48→50 Å / Num. all: 44845 / Num. obs: 44396 / % possible obs: 99 % / Observed criterion σ(F): 2 / Observed criterion σ(I): 2
Reflection shellResolution: 2.48→2.62 Å / Redundancy: 3.8 % / Mean I/σ(I) obs: 2.35 / % possible all: 98.3

-
Processing

Software
NameVersionClassification
ADSCQuantumdata collection
PHASERphasing
PHENIX(phenix.refine: 1.7.3_928)refinement
XDSdata reduction
XDSdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 2c0t

2c0t


Resolution: 2.481→40.747 Å / Occupancy max: 1 / Occupancy min: 1 / SU ML: 0.38 / σ(F): 1.99 / Phase error: 29.32 / Stereochemistry target values: ML
RfactorNum. reflection% reflectionSelection details
Rfree0.2811 2219 5 %random
Rwork0.226 ---
all0.2811 44396 --
obs0.2288 44385 99 %-
Solvent computationShrinkage radii: 0.73 Å / VDW probe radii: 1 Å / Solvent model: FLAT BULK SOLVENT MODEL / Bsol: 28.425 Å2 / ksol: 0.341 e/Å3
Displacement parametersBiso max: 100.7 Å2 / Biso mean: 43.4565 Å2 / Biso min: 15.17 Å2
Baniso -1Baniso -2Baniso -3
1-0.5412 Å2-0 Å20.1013 Å2
2---0.5572 Å2-0 Å2
3---0.016 Å2
Refinement stepCycle: LAST / Resolution: 2.481→40.747 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6991 0 60 237 7288
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0097224
X-RAY DIFFRACTIONf_angle_d1.219765
X-RAY DIFFRACTIONf_chiral_restr0.0791034
X-RAY DIFFRACTIONf_plane_restr0.0051240
X-RAY DIFFRACTIONf_dihedral_angle_d15.7862725
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 16

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2.4808-2.53470.37841370.30422614275198
2.5347-2.59370.33231390.28552632277199
2.5937-2.65850.35211350.28532573270899
2.6585-2.73040.36511380.28612614275299
2.7304-2.81070.33341370.27672609274699
2.8107-2.90140.36041380.26012617275599
2.9014-3.00510.3271380.26082629276799
3.0051-3.12530.32911380.24382606274499
3.1253-3.26750.29751390.23342660279999
3.2675-3.43970.3071380.22072620275899
3.4397-3.65510.22741390.21672626276599
3.6551-3.93710.2551390.20012654279399
3.9371-4.33290.23421400.18212655279599
4.3329-4.95890.22631400.17742658279899
4.9589-6.24410.26271400.22712666280699
6.2441-40.75220.27971440.22752733287799

+
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