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- PDB-9ks9: Crystal structure of MerTK kinase domain in complex with compound 6 -

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Basic information

Entry
Database: PDB / ID: 9ks9
TitleCrystal structure of MerTK kinase domain in complex with compound 6
ComponentsTyrosine-protein kinase Mer
KeywordsTRANSFERASE / kinase / dynamic dimer / Complex / TAM / Immune regulation / allosteric binding inhibitor / Type 2 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 / cell-cell signaling / nervous system development / 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 / 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
Similarity search - Domain/homology
: / Tyrosine-protein kinase Mer
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.8 Å
AuthorsPeng, Y.H. / Lee, L.C. / Hsueh, C.C. / Wu, S.Y.
Funding support1items
OrganizationGrant numberCountry
Not funded
CitationJournal: J.Med.Chem. / Year: 2025
Title: Structure-Based Design of Potent and Selective MerTK Inhibitors by Modulating the Conformation of alpha C Helix.
Authors: Peng, Y.H. / Li, M.C. / Yen, W.C. / Yeh, T.K. / Hsueh, C.C. / Kuo, F.M. / Lai, Y.L. / Chang, L. / Lee, L.C. / Chen, P.Y. / Yen, K.J. / Chang, T.Y. / Sun, H.Y. / Chang, C.Y. / Hsieh, S.H. / ...Authors: Peng, Y.H. / Li, M.C. / Yen, W.C. / Yeh, T.K. / Hsueh, C.C. / Kuo, F.M. / Lai, Y.L. / Chang, L. / Lee, L.C. / Chen, P.Y. / Yen, K.J. / Chang, T.Y. / Sun, H.Y. / Chang, C.Y. / Hsieh, S.H. / Yang, C.M. / Hsieh, H.P. / Wu, S.Y.
History
DepositionNov 29, 2024Deposition site: PDBJ / Processing site: PDBJ
Revision 1.0Oct 8, 2025Provider: repository / Type: Initial release

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

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


Theoretical massNumber of molelcules
Total (without water)68,9404
Polymers67,7122
Non-polymers1,2272
Water1,00956
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area1760 Å2
ΔGint-11 kcal/mol
Surface area24450 Å2
MethodPISA
Unit cell
Length a, b, c (Å)51.560, 91.350, 69.840
Angle α, β, γ (deg.)90.00, 101.00, 90.00
Int Tables number4
Space group name H-MP1211

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Components

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


Mass: 33856.230 Da / Num. of mol.: 2 / Fragment: catalytic domain
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: MERTK, MER / Plasmid: pET28a / Production host: Escherichia coli BL21(DE3) (bacteria)
Variant (production host): BL21(DE3)pLysS Escherichia coli pLysS
References: UniProt: Q12866, receptor protein-tyrosine kinase
#2: Chemical ChemComp-A1L6L / ~{N}-[4-[5-(3-aminophenyl)-6-(1-methylpyrazol-4-yl)furo[2,3-d]pyrimidin-4-yl]oxyphenyl]-1-(4-fluorophenyl)-2-oxidanylidene-pyridine-3-carboxamide


Mass: 613.597 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C34H24FN7O4 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 56 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationN

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Experimental details

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Experiment

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

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Sample preparation

CrystalDensity Matthews: 2.38 Å3/Da / Density % sol: 48.41 %
Crystal growTemperature: 291 K / Method: vapor diffusion, hanging drop / pH: 6.4
Details: 24% PEG 200, 0.05 M Calcium chloride dehydrate, 0.1 M MES monohydrate pH 6.4
PH range: 6.1-7.8

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: NSRRC / Beamline: TPS 05A / Wavelength: 0.99984 Å
DetectorType: DECTRIS EIGER2 X 9M / Detector: PIXEL / Date: Feb 25, 2020
RadiationMonochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.99984 Å / Relative weight: 1
ReflectionResolution: 2.8→45.675 Å / Num. obs: 14613 / % possible obs: 92.8163 % / Redundancy: 9.8 % / CC1/2: 0.992 / Rrim(I) all: 0.125 / Net I/av σ(I): 14.39 / Net I/σ(I): 14.39
Reflection shellResolution: 2.8→3.53 Å / Redundancy: 9.7 % / Mean I/σ(I) obs: 6.77 / Num. unique obs: 2383 / CC1/2: 0.976 / Rrim(I) all: 0.253 / % possible all: 94.7

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Processing

Software
NameVersionClassification
PHENIX(1.20.1_4487: ???)refinement
Aimlessdata scaling
XDSdata reduction
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 3TCP

3tcp


Resolution: 2.8→34.28 Å / SU ML: 0.4 / Cross valid method: FREE R-VALUE / σ(F): 1.42 / Phase error: 28.45 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2603 1459 10.01 %
Rwork0.2063 --
obs0.2118 14572 92.6 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.8→34.28 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4000 0 92 56 4148
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.002
X-RAY DIFFRACTIONf_angle_d0.62
X-RAY DIFFRACTIONf_dihedral_angle_d7.167566
X-RAY DIFFRACTIONf_chiral_restr0.04645
X-RAY DIFFRACTIONf_plane_restr0.004707
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.8-2.90.36591460.27751320X-RAY DIFFRACTION94
2.9-3.020.30681480.23221329X-RAY DIFFRACTION95
3.02-3.150.32441500.22671344X-RAY DIFFRACTION95
3.15-3.320.3121450.22591307X-RAY DIFFRACTION93
3.32-3.530.29721460.22651315X-RAY DIFFRACTION93
3.53-3.80.25511460.18951312X-RAY DIFFRACTION93
3.8-4.180.20811460.17161315X-RAY DIFFRACTION92
4.18-4.780.19391460.16651312X-RAY DIFFRACTION92
4.79-6.020.25991440.20351297X-RAY DIFFRACTION91
6.02-8.40.2561420.22791262X-RAY DIFFRACTION87

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