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- PDB-7p6q: ROCK2 IN COMPLEX WITH COMPOUND 21 -

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Basic information

Entry
Database: PDB / ID: 7p6q
TitleROCK2 IN COMPLEX WITH COMPOUND 21
ComponentsRho-associated protein kinase 2
KeywordsTRANSFERASE / Rho-associated protein kinase 2 / inhibitor complex
Function / homology
Function and homology information


positive regulation of connective tissue growth factor production / cellular response to acetylcholine / positive regulation of fibroblast growth factor production / positive regulation of centrosome duplication / regulation of angiotensin-activated signaling pathway / negative regulation of protein localization to lysosome / regulation of keratinocyte differentiation / Rho-dependent protein serine/threonine kinase activity / positive regulation of connective tissue replacement / response to transforming growth factor beta ...positive regulation of connective tissue growth factor production / cellular response to acetylcholine / positive regulation of fibroblast growth factor production / positive regulation of centrosome duplication / regulation of angiotensin-activated signaling pathway / negative regulation of protein localization to lysosome / regulation of keratinocyte differentiation / Rho-dependent protein serine/threonine kinase activity / positive regulation of connective tissue replacement / response to transforming growth factor beta / positive regulation of amyloid precursor protein catabolic process / regulation of cell junction assembly / regulation of nervous system process / positive regulation of protein localization to early endosome / host-mediated perturbation of viral process / cellular response to testosterone stimulus / embryonic morphogenesis / regulation of cellular response to hypoxia / negative regulation of nitric oxide biosynthetic process / regulation of cell motility / negative regulation of biomineral tissue development / regulation of establishment of endothelial barrier / response to angiotensin / regulation of stress fiber assembly / RHO GTPases Activate ROCKs / actomyosin structure organization / Sema4D induced cell migration and growth-cone collapse / aortic valve morphogenesis / cortical actin cytoskeleton organization / RHOBTB1 GTPase cycle / tau-protein kinase activity / regulation of focal adhesion assembly / regulation of establishment of cell polarity / negative regulation of bicellular tight junction assembly / RHOB GTPase cycle / positive regulation of amyloid-beta formation / EPHA-mediated growth cone collapse / positive regulation of cardiac muscle hypertrophy / RHOC GTPase cycle / mRNA destabilization / centrosome duplication / mitotic cytokinesis / RHOH GTPase cycle / smooth muscle contraction / epithelial to mesenchymal transition / RHOA GTPase cycle / endopeptidase activator activity / regulation of cell adhesion / Rho protein signal transduction / positive regulation of stress fiber assembly / EPHB-mediated forward signaling / positive regulation of endothelial cell migration / negative regulation of angiogenesis / blood vessel diameter maintenance / response to ischemia / protein localization to plasma membrane / regulation of actin cytoskeleton organization / regulation of circadian rhythm / small GTPase binding / VEGFA-VEGFR2 Pathway / tau protein binding / cytoplasmic ribonucleoprotein granule / positive regulation of protein phosphorylation / rhythmic process / G alpha (12/13) signalling events / actin cytoskeleton organization / protease binding / Potential therapeutics for SARS / cytoskeleton / protein phosphorylation / non-specific serine/threonine protein kinase / positive regulation of MAPK cascade / positive regulation of cell migration / negative regulation of gene expression / protein serine kinase activity / protein serine/threonine kinase activity / centrosome / positive regulation of gene expression / structural molecule activity / RNA binding / zinc ion binding / ATP binding / nucleus / plasma membrane / cytosol / cytoplasm
Similarity search - Function
: / Rho-associated protein kinase 2, HR1 domain / ROCK, Rho binding domain / Rho-associated protein kinase 1/2 / Rho Binding / Rho-binding (RhoBD) domain profile. / MRCK kinase PH domain / : / HR1 rho-binding domain / REM-1 domain profile. ...: / Rho-associated protein kinase 2, HR1 domain / ROCK, Rho binding domain / Rho-associated protein kinase 1/2 / Rho Binding / Rho-binding (RhoBD) domain profile. / MRCK kinase PH domain / : / HR1 rho-binding domain / REM-1 domain profile. / Zinc finger phorbol-ester/DAG-type profile. / Protein kinase C conserved region 1 (C1) domains (Cysteine-rich domains) / Protein kinase C-like, phorbol ester/diacylglycerol-binding domain / C1-like domain superfamily / Extension to Ser/Thr-type protein kinases / AGC-kinase, C-terminal / AGC-kinase C-terminal domain profile. / PH domain profile. / Pleckstrin homology domain. / Pleckstrin homology domain / PH-like domain superfamily / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain / Serine/Threonine protein kinases, catalytic domain / Protein kinase, ATP binding site / Protein kinases ATP-binding region signature. / Protein kinase domain profile. / Protein kinase domain / Protein kinase-like domain superfamily
Similarity search - Domain/homology
: / Rho-associated protein kinase 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.89 Å
AuthorsMaillard, M.C.
CitationJournal: J.Med.Chem. / Year: 2022
Title: Identification of a Potent, Selective, and Brain-Penetrant Rho Kinase Inhibitor and its Activity in a Mouse Model of Huntington's Disease.
Authors: Ladduwahetty, T. / Lee, M.R. / Maillard, M.C. / Cachope, R. / Todd, D. / Barnes, M. / Beaumont, V. / Chauhan, A. / Gallati, C. / Haughan, A.F. / Kempf, G. / Luckhurst, C.A. / Matthews, K. / ...Authors: Ladduwahetty, T. / Lee, M.R. / Maillard, M.C. / Cachope, R. / Todd, D. / Barnes, M. / Beaumont, V. / Chauhan, A. / Gallati, C. / Haughan, A.F. / Kempf, G. / Luckhurst, C.A. / Matthews, K. / McAllister, G. / Mitchell, P. / Patel, H. / Rose, M. / Saville-Stones, E. / Steinbacher, S. / Stott, A.J. / Thatcher, E. / Tierney, J. / Urbonas, L. / Munoz-Sanjuan, I. / Dominguez, C.
History
DepositionJul 16, 2021Deposition site: PDBE / Processing site: PDBE
Revision 1.0Oct 22, 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: Rho-associated protein kinase 2
B: Rho-associated protein kinase 2
C: Rho-associated protein kinase 2
D: Rho-associated protein kinase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)184,2378
Polymers182,8044
Non-polymers1,4344
Water45025
1
A: Rho-associated protein kinase 2
D: Rho-associated protein kinase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)92,1194
Polymers91,4022
Non-polymers7172
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3680 Å2
ΔGint-26 kcal/mol
Surface area35890 Å2
MethodPISA
2
B: Rho-associated protein kinase 2
C: Rho-associated protein kinase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)92,1194
Polymers91,4022
Non-polymers7172
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3710 Å2
ΔGint-26 kcal/mol
Surface area36050 Å2
MethodPISA
Unit cell
Length a, b, c (Å)150.628, 132.544, 92.178
Angle α, β, γ (deg.)90.000, 109.070, 90.000
Int Tables number5
Space group name H-MC121
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21B
12A
22C
13A
23D
14B
24C
15B
25D
16C
26D

NCS domain segments:

Component-ID: _ / Beg auth comp-ID: ALA / Beg label comp-ID: ALA / End auth comp-ID: ARG / End label comp-ID: ARG / Refine code: _ / Auth seq-ID: 24 - 417 / Label seq-ID: 6 - 399

Dom-IDEns-IDAuth asym-IDLabel asym-ID
11AA
21BB
12AA
22CC
13AA
23DD
14BB
24CC
15BB
25DD
16CC
26DD

NCS ensembles :
ID
1
2
3
4
5
6

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Components

#1: Protein
Rho-associated protein kinase 2 / Rho kinase 2 / Rho-associated / coiled-coil-containing protein kinase 2 / coiled-coil-containing ...Rho kinase 2 / Rho-associated / coiled-coil-containing protein kinase 2 / coiled-coil-containing protein kinase II / ROCK-II / p164 ROCK-2


Mass: 45700.914 Da / Num. of mol.: 4 / Fragment: KINASE DOMAIN
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ROCK2, KIAA0619 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: O75116, non-specific serine/threonine protein kinase
#2: Chemical
ChemComp-5YO / 4-(3-fluoranylpyridin-4-yl)-~{N}-[(1~{R})-1-(3-methoxyphenyl)ethyl]piperazine-1-carboxamide


Mass: 358.410 Da / Num. of mol.: 4 / Source method: obtained synthetically / Formula: C19H23FN4O2 / Feature type: SUBJECT OF INVESTIGATION
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 25 / 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: 2.45 Å3/Da / Density % sol: 49.88 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / Details: PEG6000, LiCl, MES/NaOH

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Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 0.99996 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Nov 27, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.99996 Å / Relative weight: 1
ReflectionResolution: 2.89→97.01 Å / Num. obs: 38003 / % possible obs: 98.9 % / Redundancy: 3.2 % / Biso Wilson estimate: 75.745 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.051 / Rrim(I) all: 0.062 / Χ2: 1.034 / Net I/σ(I): 16.63
Reflection shellResolution: 2.89→97.01 Å / Redundancy: 3.3 % / Rmerge(I) obs: 0.442 / Mean I/σ(I) obs: 3.01 / Num. unique obs: 148 / CC1/2: 0.997 / Rrim(I) all: 0.03 / % possible all: 98.7

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Processing

Software
NameVersionClassification
XSCALEdata scaling
REFMAC5.8.0049refinement
PDB_EXTRACT3.27data extraction
XDSdata reduction
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: NONE

Resolution: 2.89→97.01 Å / Cor.coef. Fo:Fc: 0.941 / Cor.coef. Fo:Fc free: 0.916 / SU B: 21.709 / SU ML: 0.399 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.437 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2659 634 1.7 %RANDOM
Rwork0.2078 ---
obs0.2088 37369 99.08 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 199.08 Å2 / Biso mean: 68.451 Å2 / Biso min: 32.97 Å2
Baniso -1Baniso -2Baniso -3
1--2.3 Å2-0 Å2-1.62 Å2
2--4.55 Å20 Å2
3----0.91 Å2
Refinement stepCycle: final / Resolution: 2.89→97.01 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms12381 0 104 25 12510
Biso mean--57.14 53.25 -
Num. residues----1521
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.010.01912188
X-RAY DIFFRACTIONr_bond_other_d0.0010.0211153
X-RAY DIFFRACTIONr_angle_refined_deg1.3351.95416575
X-RAY DIFFRACTIONr_angle_other_deg2.886325415
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.40751508
X-RAY DIFFRACTIONr_dihedral_angle_2_deg33.66224.018560
X-RAY DIFFRACTIONr_dihedral_angle_3_deg15.00915.0431842
X-RAY DIFFRACTIONr_dihedral_angle_4_deg21.9671560
X-RAY DIFFRACTIONr_chiral_restr0.070.21796
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.02114005
X-RAY DIFFRACTIONr_gen_planes_other0.0040.022915
Refine LS restraints NCS

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

Ens-IDDom-IDAuth asym-IDNumberRms dev position (Å)
11A201540.07
12B201540.07
21A208850.08
22C208850.08
31A209490.06
32D209490.06
41B199740.07
42C199740.07
51B202070.05
52D202070.05
61C217470.07
62D217470.07
LS refinement shellResolution: 2.89→2.965 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.449 52 -
Rwork0.392 2680 -
all-2732 -
obs--96.61 %

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