[English] 日本語
Yorodumi
- PDB-5k0k: Crystal structure of the catalytic domain of the proto-oncogene t... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5k0k
TitleCrystal structure of the catalytic domain of the proto-oncogene tyrosine-protein kinase MER in complex with inhibitor UNC2434
ComponentsTyrosine-protein kinase Mer
KeywordsTransferase/Transferase Inhibitor / Macrocyclic / Pyrrolopyrimidines / Drug Design / Fibrinolytic Agents / Protein Kinase Inhibitors / Proto-Oncogene Proteins / Pyrimidines / Receptor Protein-Tyrosine Kinases / Structure-Activity Relationship / Thrombosis / Transferase-Transferase Inhibitor complex
Function / homology
Function and homology information


negative regulation of leukocyte apoptotic process / negative regulation of lymphocyte activation / neutrophil clearance / natural killer cell differentiation / secretion by cell / negative regulation of cytokine production / vagina development / photoreceptor outer segment / positive regulation of phagocytosis / phagocytosis ...negative regulation of leukocyte apoptotic process / negative regulation of lymphocyte activation / neutrophil clearance / natural killer cell differentiation / secretion by cell / negative regulation of cytokine production / vagina development / photoreceptor outer segment / positive regulation of phagocytosis / phagocytosis / transmembrane receptor protein tyrosine kinase activity / substrate adhesion-dependent cell spreading / phosphatidylinositol 3-kinase/protein kinase B signal transduction / establishment of localization in cell / Cell surface interactions at the vascular wall / receptor protein-tyrosine kinase / platelet activation / cell surface receptor protein tyrosine kinase signaling pathway / cell migration / retina development in camera-type eye / cell-cell signaling / nervous system development / spermatogenesis / cell surface receptor signaling pathway / receptor complex / protein phosphorylation / extracellular space / ATP binding / plasma membrane / cytoplasm
Similarity search - Function
Immunoglobulin / Immunoglobulin domain / Immunoglobulin domain / Fibronectin type III domain / Fibronectin type 3 domain / Fibronectin type-III domain profile. / Fibronectin type III / Fibronectin type III superfamily / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain ...Immunoglobulin / Immunoglobulin domain / Immunoglobulin domain / Fibronectin type III domain / Fibronectin type 3 domain / Fibronectin type-III domain profile. / Fibronectin type III / Fibronectin type III superfamily / Tyrosine-protein kinase, catalytic domain / Tyrosine kinase, catalytic domain / Tyrosine protein kinases specific active-site signature. / Immunoglobulin subtype / Immunoglobulin / Tyrosine-protein kinase, active site / Protein tyrosine and serine/threonine kinase / Serine-threonine/tyrosine-protein kinase, catalytic domain / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Ig-like domain profile. / Immunoglobulin-like domain / Immunoglobulin-like domain superfamily / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Immunoglobulin-like fold / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily / Orthogonal Bundle / Mainly Alpha
Similarity search - Domain/homology
Chem-6Q1 / Tyrosine-protein kinase Mer
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.545 Å
AuthorsWang, X. / Liu, J. / Zhang, W. / Stashko, M.A. / Nichols, J. / DeRyckere, D. / Miley, M.J. / Norris-Drouin, J. / Chen, Z. / Machius, M. ...Wang, X. / Liu, J. / Zhang, W. / Stashko, M.A. / Nichols, J. / DeRyckere, D. / Miley, M.J. / Norris-Drouin, J. / Chen, Z. / Machius, M. / Wood, E. / Graham, D.K. / Earp, H.S. / Graham, K. / Kireev, D. / Frye, S.V.
CitationJournal: ACS Med Chem Lett / Year: 2016
Title: Design and Synthesis of Novel Macrocyclic Mer Tyrosine Kinase Inhibitors.
Authors: Wang, X. / Liu, J. / Zhang, W. / Stashko, M.A. / Nichols, J. / Miley, M.J. / Norris-Drouin, J. / Chen, Z. / Machius, M. / DeRyckere, D. / Wood, E. / Graham, D.K. / Earp, H.S. / Kireev, D. / Frye, S.V.
History
DepositionMay 17, 2016Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 11, 2017Provider: repository / Type: Initial release
Revision 1.1Sep 27, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description / Structure summary
Category: chem_comp / chem_comp_atom ...chem_comp / chem_comp_atom / chem_comp_bond / database_2 / entity / pdbx_entity_nonpoly / pdbx_initial_refinement_model
Item: _chem_comp.name / _database_2.pdbx_DOI ..._chem_comp.name / _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _entity.pdbx_description / _pdbx_entity_nonpoly.name

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

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


Theoretical massNumber of molelcules
Total (without water)72,93911
Polymers71,7792
Non-polymers1,1609
Water50428
1
A: Tyrosine-protein kinase Mer
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,4936
Polymers35,8891
Non-polymers6035
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Tyrosine-protein kinase Mer
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,4465
Polymers35,8891
Non-polymers5574
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)51.072, 91.315, 69.203
Angle α, β, γ (deg.)90.000, 100.420, 90.000
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Tyrosine-protein kinase Mer / Proto-oncogene c-Mer / Receptor tyrosine kinase MerTK


Mass: 35889.434 Da / Num. of mol.: 2 / Fragment: catalytic domain, UNP residues 570-864
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MERTK, MER / Production host: Escherichia coli (E. coli)
References: UniProt: Q12866, receptor protein-tyrosine kinase
#2: Chemical
ChemComp-CL / CHLORIDE ION / Chloride


Mass: 35.453 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: Cl
#3: Chemical ChemComp-6Q1 / 15-{4-[(4-methylpiperazin-1-yl)methyl]phenyl}-4,5,6,7,9,10,11,12-octahydro-2,16-(azenometheno)pyrrolo[2,1-d][1,3,5,9]te traazacyclotetradecin-8(3H)-one / UNC2434


Mass: 461.602 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C26H35N7O
#4: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Formula: Mg
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 28 / 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: 2.21 Å3/Da / Density % sol: 44.37 %
Crystal growTemperature: 285.2 K / Method: vapor diffusion, sitting drop / pH: 8.5
Details: Protein at 32.5 mg/mL (in 20 mM Tris pH 8.0, 500 mM NaCl, 2mM BME) was incubated overnight with inhibitor at 2.5 mM final concentration, and then was mixed 1:1 with crystallization solution ...Details: Protein at 32.5 mg/mL (in 20 mM Tris pH 8.0, 500 mM NaCl, 2mM BME) was incubated overnight with inhibitor at 2.5 mM final concentration, and then was mixed 1:1 with crystallization solution (27-33% (v/v) Peg 400, 200 mM MgCl2, 100 mM Tris pH 8.5).

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 22-BM / Wavelength: 0.9792 Å
DetectorType: MARMOSAIC 225 mm CCD / Detector: CCD / Date: Dec 12, 2012
RadiationMonochromator: Si(220) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9792 Å / Relative weight: 1
ReflectionResolution: 2.545→34.55 Å / Num. obs: 20516 / % possible obs: 99.8 % / Observed criterion σ(F): -3 / Observed criterion σ(I): -3 / Redundancy: 4.2 % / Biso Wilson estimate: 35.7 Å2 / Rmerge(I) obs: 0.086 / Net I/σ(I): 7.9
Reflection shellResolution: 2.545→2.57 Å / Redundancy: 3.8 % / Rmerge(I) obs: 0.686 / Mean I/σ(I) obs: 1.9 / % possible all: 96

-
Processing

Software
NameVersionClassification
PHENIXdev_1261refinement
PDB_EXTRACT3.2data extraction
HKL-2000data reduction
SCALEPACKdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3BRB

3brb


Resolution: 2.545→34.547 Å / SU ML: 0.31 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 26.97
RfactorNum. reflection% reflectionSelection details
Rfree0.2543 1772 10 %Random selection
Rwork0.1979 ---
obs0.2035 17714 86.05 %-
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å
Displacement parametersBiso max: 209.51 Å2 / Biso mean: 56.6 Å2 / Biso min: 20.53 Å2
Refinement stepCycle: final / Resolution: 2.545→34.547 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4076 0 145 28 4249
Biso mean--57.12 36.25 -
Num. residues----508
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0044276
X-RAY DIFFRACTIONf_angle_d0.725782
X-RAY DIFFRACTIONf_chiral_restr0.043640
X-RAY DIFFRACTIONf_plane_restr0.003722
X-RAY DIFFRACTIONf_dihedral_angle_d13.7991650
LS refinement shell

Refine-ID: X-RAY DIFFRACTION / Total num. of bins used: 13

Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkNum. reflection all% reflection obs (%)
2.5446-2.61340.2717690.238761768644
2.6134-2.69020.3441850.245876985454
2.6902-2.7770.31921010.2399910101165
2.777-2.87620.29351160.23651045116173
2.8762-2.99130.32581330.23941197133085
2.9913-3.12740.31891540.24151380153498
3.1274-3.29210.34571580.232314231581100
3.2921-3.49820.27891570.199514131570100
3.4982-3.7680.22561600.185714381598100
3.768-4.14660.2241590.168414281587100
4.1466-4.74540.18311580.159914271585100
4.7454-5.97360.20761590.176214341593100
5.9736-34.54980.23541630.192514611624100
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)
18.1120.05871.78268.98550.50279.44330.1617-0.6049-0.4162-0.0165-0.0011-0.51120.31930.6197-0.19830.33930.0389-0.04790.4068-0.04770.334410.8882-9.369419.0199
24.70530.86584.14860.3790.46013.9801-0.6445-0.31910.32930.0186-0.0298-0.56040.07840.95120.29630.33930.0619-0.14570.8161-0.0410.525315.4194-2.047725.3059
33.5886-4.68114.43337.0578-3.94878.86640.37310.65180.06270.6522-0.2473-0.81-0.1661.4965-0.12970.54090.01420.04570.5161-0.05730.46756.643-4.35433.4314
42.5908-1.0789-1.21474.2866-0.21912.94710.0311-0.1054-0.221-0.25590.14550.10370.20460.1161-0.19780.2118-0.0362-0.0190.24230.00160.2538-2.48184.113123.8314
54.5398-0.1019-0.655.5246-0.13345.68270.1998-0.35040.3940.4138-0.0403-0.6326-0.69940.5306-0.15670.2444-0.0726-0.02350.336-0.00830.37940.468619.773832.604
64.94230.9277-0.0055.9934-0.76663.98370.0484-0.2144-0.01360.22520.18020.1548-0.4129-0.5894-0.19610.22450.03020.11010.32380.01550.2554-13.118916.546834.6716
75.6950.3533-2.41813.9328-1.53275.81550.09530.31730.2254-0.31620.1542-0.0873-0.42020.7967-0.24920.3275-0.1135-0.03870.501-0.06710.309810.731651.422417.7656
84.5042.78752.65884.5111.43332.6625-0.17360.01430.06070.04820.1085-0.01710.09670.91890.09040.338-0.05230.00290.54140.00920.239410.764247.73715.2608
92.4004-0.2269-0.12185.0714-1.015.27330.01630.0676-0.0195-0.1005-0.01-0.14260.15480.12220.01090.1986-0.0427-0.00930.26010.03540.2486-1.10429.29473.7596
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1chain 'A' and (resid 577 through 612 )A577 - 612
2X-RAY DIFFRACTION2chain 'A' and (resid 613 through 628 )A613 - 628
3X-RAY DIFFRACTION3chain 'A' and (resid 629 through 651 )A629 - 651
4X-RAY DIFFRACTION4chain 'A' and (resid 652 through 763 )A652 - 763
5X-RAY DIFFRACTION5chain 'A' and (resid 764 through 814 )A764 - 814
6X-RAY DIFFRACTION6chain 'A' and (resid 815 through 863 )A815 - 863
7X-RAY DIFFRACTION7chain 'B' and (resid 577 through 643 )B577 - 643
8X-RAY DIFFRACTION8chain 'B' and (resid 644 through 678 )B644 - 678
9X-RAY DIFFRACTION9chain 'B' and (resid 679 through 862 )B679 - 862

+
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