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- PDB-8x2o: RIPK2 in complex with K252 -

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Basic information

Entry
Database: PDB / ID: 8x2o
TitleRIPK2 in complex with K252
ComponentsReceptor-interacting serine/threonine-protein kinase 2
KeywordsIMMUNE SYSTEM / inhibitor
Function / homology
Function and homology information


response to interleukin-18 / toll-like receptor 2 signaling pathway / positive regulation of T-helper 1 cell differentiation / positive regulation of cytokine-mediated signaling pathway / caspase binding / immature T cell proliferation in thymus / positive regulation of T-helper 1 type immune response / positive regulation of xenophagy / xenophagy / LIM domain binding ...response to interleukin-18 / toll-like receptor 2 signaling pathway / positive regulation of T-helper 1 cell differentiation / positive regulation of cytokine-mediated signaling pathway / caspase binding / immature T cell proliferation in thymus / positive regulation of T-helper 1 type immune response / positive regulation of xenophagy / xenophagy / LIM domain binding / positive regulation of protein K63-linked ubiquitination / nucleotide-binding oligomerization domain containing 1 signaling pathway / cellular response to muramyl dipeptide / positive regulation of stress-activated MAPK cascade / CARD domain binding / positive regulation of immature T cell proliferation in thymus / CD4-positive, alpha-beta T cell proliferation / cellular response to peptidoglycan / response to interleukin-12 / positive regulation of CD4-positive, alpha-beta T cell proliferation / JUN kinase kinase kinase activity / nucleotide-binding oligomerization domain containing 2 signaling pathway / positive regulation of macrophage cytokine production / toll-like receptor 4 signaling pathway / response to exogenous dsRNA / cellular response to lipoteichoic acid / positive regulation of interferon-alpha production / canonical NF-kappaB signal transduction / stress-activated MAPK cascade / positive regulation of peptidyl-tyrosine phosphorylation / positive regulation of chemokine production / JNK cascade / signaling adaptor activity / positive regulation of interleukin-12 production / ERK1 and ERK2 cascade / positive regulation of interleukin-2 production / response to interleukin-1 / p75NTR recruits signalling complexes / positive regulation of interferon-beta production / lipopolysaccharide-mediated signaling pathway / positive regulation of interleukin-1 beta production / JNK (c-Jun kinases) phosphorylation and activation mediated by activated human TAK1 / positive regulation of protein ubiquitination / activated TAK1 mediates p38 MAPK activation / non-membrane spanning protein tyrosine kinase activity / positive regulation of JNK cascade / non-specific protein-tyrosine kinase / TAK1-dependent IKK and NF-kappa-B activation / NOD1/2 Signaling Pathway / cytokine-mediated signaling pathway / protein homooligomerization / positive regulation of interleukin-6 production / positive regulation of type II interferon production / Interleukin-1 signaling / positive regulation of tumor necrosis factor production / Ovarian tumor domain proteases / Downstream TCR signaling / T cell receptor signaling pathway / vesicle / adaptive immune response / positive regulation of canonical NF-kappaB signal transduction / eukaryotic translation initiation factor 2alpha kinase activity / cytoskeleton / 3-phosphoinositide-dependent protein kinase activity / DNA-dependent protein kinase activity / ribosomal protein S6 kinase activity / histone H3S10 kinase activity / histone H2AXS139 kinase activity / histone H3S28 kinase activity / histone H4S1 kinase activity / histone H2BS14 kinase activity / histone H3T3 kinase activity / histone H2AS121 kinase activity / Rho-dependent protein serine/threonine kinase activity / histone H2BS36 kinase activity / histone H3S57 kinase activity / histone H2AT120 kinase activity / AMP-activated protein kinase activity / histone H2AS1 kinase activity / histone H3T6 kinase activity / histone H3T11 kinase activity / histone H3T45 kinase activity / positive regulation of ERK1 and ERK2 cascade / non-specific serine/threonine protein kinase / defense response to Gram-positive bacterium / defense response to bacterium / positive regulation of apoptotic process / inflammatory response / signaling receptor binding / innate immune response / protein serine kinase activity / protein serine/threonine kinase activity / apoptotic process / SARS-CoV-2 activates/modulates innate and adaptive immune responses / endoplasmic reticulum / signal transduction / protein homodimerization activity / positive regulation of transcription by RNA polymerase II / protein-containing complex / ATP binding
Similarity search - Function
Receptor-interacting serine/threonine-protein kinase 2 / RIP2, CARD domain / CARD domain / CARD caspase recruitment domain profile. / Caspase recruitment domain / : / Death-like domain superfamily / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Serine/threonine-protein kinase, active site ...Receptor-interacting serine/threonine-protein kinase 2 / RIP2, CARD domain / CARD domain / CARD caspase recruitment domain profile. / Caspase recruitment domain / : / Death-like domain superfamily / Serine-threonine/tyrosine-protein kinase, catalytic domain / Protein tyrosine and serine/threonine kinase / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Serine/Threonine protein kinases, catalytic domain / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
: / Receptor-interacting serine/threonine-protein kinase 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.26 Å
AuthorsYang, J.H. / Yang, J.H.
Funding support China, 1items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)82272647 China
CitationJournal: Acta Pharm Sin B / Year: 2025
Title: CMD-OPT model enables the discovery of a potent and selective RIPK2 inhibitor as preclinical candidate for the treatment of acute liver injury
Authors: Chen, Y. / Yuan, X. / Yan, W. / Zou, Y. / Wei, H. / Wei, Y. / Tang, M. / Chen, Y. / Ma, Z. / Yang, T. / Liu, K. / Xiong, B. / Hu, X. / Yang, J. / Chen, L.
History
DepositionNov 10, 2023Deposition site: PDBJ / Processing site: PDBC
Revision 1.0Nov 13, 2024Provider: repository / Type: Initial release
Revision 1.1May 28, 2025Group: Database references / Category: citation / citation_author
Item: _citation.country / _citation.journal_abbrev ..._citation.country / _citation.journal_abbrev / _citation.journal_id_CSD / _citation.journal_id_ISSN / _citation.pdbx_database_id_DOI / _citation.title / _citation.year

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Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

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Assembly

Deposited unit
A: Receptor-interacting serine/threonine-protein kinase 2
B: Receptor-interacting serine/threonine-protein kinase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)73,5594
Polymers72,6282
Non-polymers9312
Water2,180121
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area2710 Å2
ΔGint-17 kcal/mol
Surface area23750 Å2
MethodPISA
Unit cell
Length a, b, c (Å)61.080, 102.770, 125.310
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Space group name HallP2ac2ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x,y+1/2,-z+1/2
#4: -x+1/2,-y,z+1/2
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
d_1ens_1(chain "A" and (resid 9 through 21 or (resid 22...
d_2ens_1(chain "B" and (resid 9 through 49 or resid 57...

NCS domain segments:

Ens-ID: ens_1

Dom-IDComponent-IDBeg auth comp-IDBeg label comp-IDEnd auth comp-IDEnd label comp-IDAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
d_11ALAALASERSERAA9 - 3169 - 316
d_21ALAALALEULEUBB9 - 499 - 49
d_22ASPASPTYRTYRBB57 - 19857 - 198
d_23SERSERSERSERBB207 - 316207 - 316

NCS oper: (Code: givenMatrix: (-0.284475189667, 0.886555129202, -0.364820324748), (0.884509386902, 0.0959472284484, -0.456549311506), (-0.369752634808, -0.452563953755, -0.811460939796)Vector: 18. ...NCS oper: (Code: given
Matrix: (-0.284475189667, 0.886555129202, -0.364820324748), (0.884509386902, 0.0959472284484, -0.456549311506), (-0.369752634808, -0.452563953755, -0.811460939796)
Vector: 18.6864904284, -8.57156407689, 16.3336940371)

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Components

#1: Protein Receptor-interacting serine/threonine-protein kinase 2 / CARD-containing interleukin-1 beta-converting enzyme-associated kinase / CARD-containing IL-1 beta ...CARD-containing interleukin-1 beta-converting enzyme-associated kinase / CARD-containing IL-1 beta ICE-kinase / RIP-like-interacting CLARP kinase / Receptor-interacting protein 2 / RIP-2 / Tyrosine-protein kinase RIPK2


Mass: 36313.750 Da / Num. of mol.: 2
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: RIPK2, CARDIAK, RICK, RIP2, UNQ277/PRO314/PRO34092 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: O43353, non-specific serine/threonine protein kinase, non-specific protein-tyrosine kinase
#2: Chemical ChemComp-6IL / ~{N}-[(1~{R})-4-[4-[(6-fluoranyl-1,3-benzothiazol-5-yl)amino]thieno[2,3-d]pyrimidin-6-yl]cyclohex-3-en-1-yl]cyclopropanecarboxamide


Mass: 465.566 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C23H20FN5OS2 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 121 / 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: 2.71 Å3/Da / Density % sol: 54.57 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / Details: 100mM Mes pH7,12% PEG 400, 250mM CaCl2

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SSRF / Beamline: BL18U1 / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS3 6M / Detector: PIXEL / Date: Dec 19, 2022
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.26→54.9 Å / Num. obs: 37633 / % possible obs: 99.81 % / Redundancy: 2 % / Biso Wilson estimate: 49.1 Å2 / CC1/2: 0.999 / Rmerge(I) obs: 0.02462 / Net I/σ(I): 16.97
Reflection shellResolution: 2.26→2.341 Å / Rmerge(I) obs: 0.3625 / Mean I/σ(I) obs: 2.19 / Num. unique obs: 3690 / CC1/2: 0.729

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Processing

Software
NameVersionClassification
PHENIX1.18.2_3874refinement
PHENIX1.18.2_3874refinement
HKL-3000data reduction
xia2data scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.26→54.9 Å / SU ML: 0.3457 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 25.9393
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2544 2000 5.32 %
Rwork0.213 35625 -
obs0.2152 37625 99.81 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 54.83 Å2
Refinement stepCycle: LAST / Resolution: 2.26→54.9 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4356 0 64 121 4541
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00964550
X-RAY DIFFRACTIONf_angle_d1.19246223
X-RAY DIFFRACTIONf_chiral_restr0.0662702
X-RAY DIFFRACTIONf_plane_restr0.009783
X-RAY DIFFRACTIONf_dihedral_angle_d21.90051738
Refine LS restraints NCSType: Torsion NCS / Rms dev position: 0.992252773739 Å
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.26-2.320.36391390.30022474X-RAY DIFFRACTION99.69
2.32-2.380.33391400.27582500X-RAY DIFFRACTION99.74
2.38-2.450.28821420.25712532X-RAY DIFFRACTION99.78
2.45-2.530.28881400.24242489X-RAY DIFFRACTION99.77
2.53-2.620.2821420.23782522X-RAY DIFFRACTION99.89
2.62-2.720.27421420.24112521X-RAY DIFFRACTION99.96
2.72-2.850.26911420.23042540X-RAY DIFFRACTION99.96
2.85-30.28751410.22732511X-RAY DIFFRACTION100
3-3.190.26691430.22942537X-RAY DIFFRACTION99.85
3.19-3.430.27811420.22542556X-RAY DIFFRACTION100
3.43-3.780.28311430.20782551X-RAY DIFFRACTION99.89
3.78-4.320.19791460.17872575X-RAY DIFFRACTION99.93
4.32-5.450.2151450.17952610X-RAY DIFFRACTION99.93
5.45-54.90.25471530.2192707X-RAY DIFFRACTION99.17
Refinement TLS params.Method: refined / Origin x: 16.7551571727 Å / Origin y: 5.46284378206 Å / Origin z: 4.33972271639 Å
111213212223313233
T0.364339891587 Å2-0.00928890033337 Å2-0.0201796528665 Å2-0.331518044041 Å20.0193084273121 Å2--0.330459071538 Å2
L1.40690499799 °2-1.42614067318 °2-0.995332176704 °2-2.8446991184 °21.69018194215 °2--1.61525491609 °2
S-0.151684211876 Å °-0.116300830463 Å °-0.271589262521 Å °0.42140819495 Å °0.0636226199657 Å °0.268912630817 Å °0.381310811982 Å °0.0202053225784 Å °0.0822550447389 Å °
Refinement TLS groupSelection details: all

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