[English] 日本語
Yorodumi
- PDB-7ab2: Crystal structure of MerTK kinase domain in complex with UNC2025 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7ab2
TitleCrystal structure of MerTK kinase domain in complex with UNC2025
ComponentsTyrosine-protein kinase Mer
KeywordsTRANSFERASE / tyrosine kinase inhibitor / structure-based drug design / type 1 inhibitor
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 / phagocytosis / transmembrane receptor protein tyrosine kinase activity ...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 / phagocytosis / transmembrane receptor protein tyrosine kinase activity / substrate adhesion-dependent cell spreading / positive regulation of phagocytosis / cell surface receptor protein tyrosine kinase signaling pathway / Cell surface interactions at the vascular wall / establishment of localization in cell / receptor protein-tyrosine kinase / platelet activation / cell migration / nervous system development / cell-cell signaling / retina development in camera-type eye / spermatogenesis / cell surface receptor signaling pathway / protein phosphorylation / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor complex / 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 ...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 / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / 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 / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-R6N / Tyrosine-protein kinase Mer
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / molecular replacement / Resolution: 1.78 Å
AuthorsPflug, A. / Schimpl, M. / McCoull, W. / Nissink, J.W.M. / Overman, R.C. / Rawlins, P.B. / Truman, C. / Underwood, E. / Warwicker, J. / Winter-Holt, J.
CitationJournal: Biochem.J. / Year: 2020
Title: A-loop interactions in Mer tyrosine kinase give rise to inhibitors with two-step mechanism and long residence time of binding.
Authors: Pflug, A. / Schimpl, M. / Nissink, J.W.M. / Overman, R.C. / Rawlins, P.B. / Truman, C. / Underwood, E. / Warwicker, J. / Winter-Holt, J. / McCoull, W.
History
DepositionSep 5, 2020Deposition site: PDBE / Processing site: PDBE
Revision 1.0Oct 28, 2020Provider: repository / Type: Initial release
Revision 1.1Nov 4, 2020Group: Database references / Category: citation / Item: _citation.pdbx_database_id_DOI
Revision 1.2Nov 11, 2020Group: Database references / Category: citation / citation_author
Item: _citation.pdbx_database_id_PubMed / _citation_author.identifier_ORCID / _citation_author.name
Revision 1.3Dec 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 1.4Jan 31, 2024Group: 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: Tyrosine-protein kinase Mer
hetero molecules


Theoretical massNumber of molelcules
Total (without water)35,1568
Polymers34,3821
Non-polymers7757
Water1,60389
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: mass spectrometry
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area950 Å2
ΔGint-33 kcal/mol
Surface area14110 Å2
Unit cell
Length a, b, c (Å)91.849, 92.040, 71.621
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number20
Space group name H-MC2221

-
Components

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


Mass: 34381.754 Da / Num. of mol.: 1 / Fragment: MERTK kinase domain / Mutation: K591R, K693R, K702R, K856R
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MERTK, MER / Production host: Escherichia coli BL21(DE3) (bacteria) / Variant (production host): Star
References: UniProt: Q12866, receptor protein-tyrosine kinase
#2: Chemical ChemComp-R6N / 4-[2-(butylamino)-5-[4-[(4-methylpiperazin-1-yl)methyl]phenyl]pyrrolo[2,3-d]pyrimidin-7-yl]cyclohexan-1-ol


Mass: 476.657 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C28H40N6O / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: Cl
#4: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 89 / 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: 2.2 Å3/Da / Density % sol: 44.12 %
Crystal growTemperature: 293 K / Method: vapor diffusion / pH: 8.5 / Details: 0.1M Tris pH 8.5, 4.3M NaCl

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I04 / Wavelength: 0.979499 Å
DetectorType: DECTRIS EIGER X 16M / Detector: PIXEL / Date: Feb 7, 2020
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.979499 Å / Relative weight: 1
ReflectionResolution: 1.778→48.139 Å / Num. obs: 18168 / % possible obs: 93.8 % / Redundancy: 6.6 % / CC1/2: 1 / Rmerge(I) obs: 0.037 / Rpim(I) all: 0.016 / Rrim(I) all: 0.04 / Net I/σ(I): 21
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsNum. measured allNum. unique obsCC1/2Rpim(I) allRrim(I) allNet I/σ(I) obs% possible all
1.778-1.9625.81.07552999080.6350.4831.1811.564
5.848-48.13960.018547790710.0080.01966.599.6

-
Phasing

PhasingMethod: molecular replacement

-
Processing

Software
NameVersionClassificationNB
XDSdata reduction
Aimlessdata scaling
AMoREphasing
REFMAC5.8.0135refinement
PDB_EXTRACT3.25data extraction
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: pdbid 3BRB

3brb


Resolution: 1.78→48.139 Å / Cor.coef. Fo:Fc: 0.963 / Cor.coef. Fo:Fc free: 0.935 / SU B: 4.338 / SU ML: 0.129 / SU R Cruickshank DPI: 0.2169 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.217 / ESU R Free: 0.193 / Stereochemistry target values: MAXIMUM LIKELIHOOD / Details: BUSTER
RfactorNum. reflection% reflectionSelection details
Rfree0.2497 893 4.9 %RANDOM
Rwork0.1933 ---
obs0.196 17267 61.46 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 134.56 Å2 / Biso mean: 48.966 Å2 / Biso min: 23.05 Å2
Baniso -1Baniso -2Baniso -3
1--0.02 Å2-0 Å2-0 Å2
2--0.34 Å20 Å2
3----0.32 Å2
Refinement stepCycle: final / Resolution: 1.78→48.139 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2124 0 47 89 2260
Biso mean--78.6 48.04 -
Num. residues----270
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0130.0192229
X-RAY DIFFRACTIONr_bond_other_d0.0020.022128
X-RAY DIFFRACTIONr_angle_refined_deg1.5171.9643020
X-RAY DIFFRACTIONr_angle_other_deg0.9792.9624887
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.1965271
X-RAY DIFFRACTIONr_dihedral_angle_2_deg35.42923.40494
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.94415381
X-RAY DIFFRACTIONr_dihedral_angle_4_deg20.621516
X-RAY DIFFRACTIONr_chiral_restr0.0850.2339
X-RAY DIFFRACTIONr_gen_planes_refined0.0060.022461
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02489
LS refinement shellResolution: 1.78→1.825 Å / Rfactor Rfree error: 0
RfactorNum. reflection% reflection
Rfree0.284 5 -
Rwork0.409 36 -
obs--1.89 %

+
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