[English] 日本語
Yorodumi
- PDB-5tc0: Structure-based optimization of 1H-imidazole-2-carboxamides as Ax... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5tc0
TitleStructure-based optimization of 1H-imidazole-2-carboxamides as Axl kinase inhibitors utilizing a Mer mutant surrogate
ComponentsTyrosine-protein kinase Mer
KeywordsTransferase/Transferase Inhibitor / kinase / inhibitor / surrogate / oncology / 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 / phagocytosis / positive regulation of 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 / phagocytosis / positive regulation of phagocytosis / transmembrane receptor protein tyrosine kinase activity / substrate adhesion-dependent cell spreading / establishment of localization in cell / Cell surface interactions at the vascular wall / receptor protein-tyrosine kinase / platelet activation / cell migration / cell-cell signaling / retina development in camera-type eye / nervous system development / spermatogenesis / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / receptor complex / cell surface receptor signaling pathway / 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 ...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. / Tyrosine-protein kinase, active site / Immunoglobulin subtype / Immunoglobulin / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / 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-79Y / Tyrosine-protein kinase Mer
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.24 Å
AuthorsHoffman, I.D. / Lawson, J.D.
CitationJournal: Bioorg. Med. Chem. Lett. / Year: 2017
Title: Structure-based optimization of 1H-imidazole-2-carboxamides as Axl kinase inhibitors utilizing a Mer mutant surrogate.
Authors: Keung, W. / Boloor, A. / Brown, J. / Kiryanov, A. / Gangloff, A. / Lawson, J.D. / Skene, R. / Hoffman, I. / Atienza, J. / Kahana, J. / De Jong, R. / Farrell, P. / Balakrishna, D. / Halkowycz, P.
History
DepositionSep 13, 2016Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 25, 2017Provider: repository / Type: Initial release
Revision 1.1Mar 6, 2024Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / struct_ncs_dom_lim
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_ncs_dom_lim.beg_auth_comp_id / _struct_ncs_dom_lim.beg_label_asym_id / _struct_ncs_dom_lim.beg_label_comp_id / _struct_ncs_dom_lim.beg_label_seq_id / _struct_ncs_dom_lim.end_auth_comp_id / _struct_ncs_dom_lim.end_label_asym_id / _struct_ncs_dom_lim.end_label_comp_id / _struct_ncs_dom_lim.end_label_seq_id

-
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)72,4233
Polymers71,9892
Non-polymers4341
Water61334
1
A: Tyrosine-protein kinase Mer
hetero molecules


Theoretical massNumber of molelcules
Total (without water)36,4282
Polymers35,9951
Non-polymers4341
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Tyrosine-protein kinase Mer


Theoretical massNumber of molelcules
Total (without water)35,9951
Polymers35,9951
Non-polymers00
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)50.406, 91.503, 69.543
Angle α, β, γ (deg.)90.000, 99.470, 90.000
Int Tables number4
Space group name H-MP1211
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21B
12A
22B
13A
23B
14A
24B
15A
25B

NCS domain segments:

Component-ID: _ / Refine code: _

Dom-IDEns-IDBeg auth comp-IDBeg label comp-IDEnd auth comp-IDEnd label comp-IDAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
11GLUGLUILEILEAA578 - 59228 - 42
21GLUGLUILEILEBB578 - 59228 - 42
12SERSERLYSLYSAA600 - 61950 - 69
22SERSERLYSLYSBB600 - 61950 - 69
13METMETCYSCYSAA641 - 65691 - 106
23METMETCYSCYSBB641 - 65691 - 106
14LYSLYSASPASPAA666 - 741116 - 191
24LYSLYSASPASPBB666 - 741116 - 191
15THRTHRSERSERAA778 - 860228 - 310
25THRTHRSERSERBB778 - 860228 - 310

NCS ensembles :
ID
1
2
3
4
5

-
Components

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


Mass: 35994.551 Da / Num. of mol.: 2 / Fragment: UNP residues 570-864
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MERTK, MER / Plasmid: pSX71 / Production host: Escherichia coli (E. coli) / Strain (production host): BL21(DE3)
References: UniProt: Q12866, receptor protein-tyrosine kinase
#2: Chemical ChemComp-79Y / N-(2-{4-[(2S)-4-(methylsulfonyl)morpholin-2-yl]-1,3-thiazol-2-yl}phenyl)-1H-imidazole-2-carboxamide


Mass: 433.505 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C18H19N5O4S2
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 34 / 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: 2.2 Å3/Da / Density % sol: 44.03 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 8.5 / Details: 29% PEG 400, 0.2M MgCl2, 0,1M Tris pH 8.5

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.3 / Wavelength: 0.9764848 Å
DetectorType: ADSC QUANTUM 315r / Detector: CCD / Date: May 27, 2010
RadiationMonochromator: Asymmetric cut single crystal Si(220) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.9764848 Å / Relative weight: 1
ReflectionResolution: 2.24→50 Å / Num. obs: 25183 / % possible obs: 84 % / Redundancy: 4.1 % / Rmerge(I) obs: 0.073 / Net I/av σ(I): 16.622 / Net I/σ(I): 10.1
Reflection shell
Resolution (Å)Redundancy (%)Rmerge(I) obsDiffraction-ID% possible all
2.24-2.2840.418150.4
2.28-2.3240.381153.7
2.32-2.3640.324157
2.36-2.4140.363160.1
2.41-2.473.90.339166.9
2.47-2.5240.319167.7
2.52-2.593.90.287176.4
2.59-2.663.90.279179.8
2.66-2.733.90.234186.8
2.73-2.8240.212190.4
2.82-2.9240.191196.7
2.92-3.044.10.161198.5
3.04-3.184.20.137198.9
3.18-3.354.20.101199
3.35-3.564.20.073199.1
3.56-3.834.20.063199.1
3.83-4.224.20.051199.3
4.22-4.824.10.045199.5
4.82-6.084.10.044199.5
6.08-504.20.035199.5

-
Processing

Software
NameVersionClassification
SCALEPACKdata scaling
REFMAC5.8.0103refinement
PDB_EXTRACT3.2data extraction
HKL-2000data reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.24→30 Å / Cor.coef. Fo:Fc: 0.942 / Cor.coef. Fo:Fc free: 0.911 / SU B: 28.687 / SU ML: 0.283 / SU R Cruickshank DPI: 0.3914 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R: 0.391 / ESU R Free: 0.259
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : WITH TLS ADDED
RfactorNum. reflection% reflectionSelection details
Rfree0.2624 1237 4.9 %RANDOM
Rwork0.2275 ---
obs0.2293 23911 83.83 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å
Displacement parametersBiso max: 116.72 Å2 / Biso mean: 56.147 Å2 / Biso min: 25.13 Å2
Baniso -1Baniso -2Baniso -3
1-6.24 Å20 Å2-4.39 Å2
2---1.71 Å2-0 Å2
3----2.91 Å2
Refinement stepCycle: final / Resolution: 2.24→30 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3939 0 29 34 4002
Biso mean--49.83 45.35 -
Num. residues----488
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0080.0194051
X-RAY DIFFRACTIONr_bond_other_d0.0030.023922
X-RAY DIFFRACTIONr_angle_refined_deg1.2951.995471
X-RAY DIFFRACTIONr_angle_other_deg1.06739042
X-RAY DIFFRACTIONr_dihedral_angle_1_deg5.9165480
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.95423.842177
X-RAY DIFFRACTIONr_dihedral_angle_3_deg14.35815749
X-RAY DIFFRACTIONr_dihedral_angle_4_deg19.1841526
X-RAY DIFFRACTIONr_chiral_restr0.0740.2613
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.0214400
X-RAY DIFFRACTIONr_gen_planes_other0.0020.02877
X-RAY DIFFRACTIONr_mcbond_it2.2984.0981944
X-RAY DIFFRACTIONr_mcbond_other2.2994.0981943
X-RAY DIFFRACTIONr_mcangle_it3.7846.1362416
Refine LS restraints NCS

Refine-ID: X-RAY DIFFRACTION / Type: interatomic distance / Weight position: 0.05

Ens-IDDom-IDAuth asym-IDNumberRms dev position (Å)
11A15140.09
12B15140.09
21A18700.11
22B18700.11
31A13060.17
32B13060.17
41A80620.11
42B80620.11
51A95220.07
52B95220.07
LS refinement shellResolution: 2.241→2.299 Å / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.289 46 -
Rwork0.314 1081 -
all-1127 -
obs--50.9 %
Refinement TLS params.Method: refined / Origin x: 18.2682 Å / Origin y: -2.8269 Å / Origin z: 15.8341 Å
111213212223313233
T0.0941 Å2-0.0032 Å20.0393 Å2-0.0139 Å20.0066 Å2--0.0718 Å2
L0.1074 °2-0.2869 °2-0.036 °2-1.7546 °20.6756 °2--1.1923 °2
S0.0229 Å °-0.0128 Å °0.0188 Å °-0.0652 Å °-0.0012 Å °0.13 Å °0.0211 Å °-0.1127 Å °-0.0217 Å °

+
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