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- PDB-7p6o: ROCK2 IN COMPLEX WITH COMPOUND 8 -

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Basic information

Entry
Database: PDB / ID: 7p6o
TitleROCK2 IN COMPLEX WITH COMPOUND 8
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 / regulation of cellular response to hypoxia / embryonic morphogenesis / 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 / regulation of establishment of cell polarity / negative regulation of bicellular tight junction assembly / tau-protein kinase activity / regulation of focal adhesion 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 / blood vessel diameter maintenance / negative regulation of angiogenesis / 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: 2.75 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
E: Rho-associated protein kinase 2
F: Rho-associated protein kinase 2
G: Rho-associated protein kinase 2
H: Rho-associated protein kinase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)368,69519
Polymers365,6078
Non-polymers3,08711
Water1,38777
1
A: Rho-associated protein kinase 2
hetero molecules

H: Rho-associated protein kinase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)92,2896
Polymers91,4022
Non-polymers8874
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation1_665x+1,y+1,z1
Buried area4470 Å2
ΔGint-26 kcal/mol
Surface area36000 Å2
MethodPISA
2
B: Rho-associated protein kinase 2
hetero molecules

C: Rho-associated protein kinase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)92,1054
Polymers91,4022
Non-polymers7032
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation1_565x,y+1,z1
Buried area3910 Å2
ΔGint-26 kcal/mol
Surface area36130 Å2
MethodPISA
3
D: Rho-associated protein kinase 2
hetero molecules

E: Rho-associated protein kinase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)92,1975
Polymers91,4022
Non-polymers7953
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation1_456x-1,y,z+11
Buried area4130 Å2
ΔGint-27 kcal/mol
Surface area36400 Å2
MethodPISA
4
F: Rho-associated protein kinase 2
hetero molecules

G: Rho-associated protein kinase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)92,1054
Polymers91,4022
Non-polymers7032
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
crystal symmetry operation1_645x+1,y-1,z1
Buried area3870 Å2
ΔGint-25 kcal/mol
Surface area36440 Å2
MethodPISA
Unit cell
Length a, b, c (Å)94.550, 101.227, 102.483
Angle α, β, γ (deg.)83.520, 73.630, 77.830
Int Tables number1
Space group name H-MP1
Noncrystallographic symmetry (NCS)NCS domain:
IDEns-IDDetails
11A
21B
12A
22C
13A
23D
14A
24E
15A
25F
16A
26G
17A
27H
18B
28C
19B
29D
110B
210E
111B
211F
112B
212G
113B
213H
114C
214D
115C
215E
116C
216F
117C
217G
118C
218H
119D
219E
120D
220F
121D
221G
122D
222H
123E
223F
124E
224G
125E
225H
126F
226G
127F
227H
128G
228H

NCS domain segments:

Component-ID: _ / End auth comp-ID: ARG / End label comp-ID: ARG / Refine code: _

Dom-IDEns-IDBeg auth comp-IDBeg label comp-IDAuth asym-IDLabel asym-IDAuth seq-IDLabel seq-ID
11SERSERAA25 - 4177 - 399
21SERSERBB25 - 4177 - 399
12ALAALAAA24 - 4176 - 399
22ALAALACC24 - 4176 - 399
13SERSERAA25 - 4177 - 399
23SERSERDD25 - 4177 - 399
14SERSERAA25 - 4177 - 399
24SERSEREE25 - 4177 - 399
15SERSERAA25 - 4177 - 399
25SERSERFF25 - 4177 - 399
16SERSERAA25 - 4177 - 399
26SERSERGG25 - 4177 - 399
17ALAALAAA24 - 4176 - 399
27ALAALAHH24 - 4176 - 399
18SERSERBB25 - 4177 - 399
28SERSERCC25 - 4177 - 399
19SERSERBB25 - 4177 - 399
29SERSERDD25 - 4177 - 399
110SERSERBB25 - 4177 - 399
210SERSEREE25 - 4177 - 399
111SERSERBB25 - 4177 - 399
211SERSERFF25 - 4177 - 399
112SERSERBB25 - 4177 - 399
212SERSERGG25 - 4177 - 399
113SERSERBB25 - 4177 - 399
213SERSERHH25 - 4177 - 399
114SERSERCC25 - 4177 - 399
214SERSERDD25 - 4177 - 399
115SERSERCC25 - 4177 - 399
215SERSEREE25 - 4177 - 399
116SERSERCC25 - 4177 - 399
216SERSERFF25 - 4177 - 399
117SERSERCC25 - 4177 - 399
217SERSERGG25 - 4177 - 399
118ALAALACC24 - 4176 - 399
218ALAALAHH24 - 4176 - 399
119SERSERDD25 - 4177 - 399
219SERSEREE25 - 4177 - 399
120SERSERDD25 - 4177 - 399
220SERSERFF25 - 4177 - 399
121SERSERDD25 - 4177 - 399
221SERSERGG25 - 4177 - 399
122SERSERDD25 - 4177 - 399
222SERSERHH25 - 4177 - 399
123SERSEREE25 - 4177 - 399
223SERSERFF25 - 4177 - 399
124SERSEREE25 - 4177 - 399
224SERSERGG25 - 4177 - 399
125SERSEREE25 - 4177 - 399
225SERSERHH25 - 4177 - 399
126SERSERFF25 - 4177 - 399
226SERSERGG25 - 4177 - 399
127SERSERFF25 - 4177 - 399
227SERSERHH25 - 4177 - 399
128SERSERGG25 - 4177 - 399
228SERSERHH25 - 4177 - 399

NCS ensembles :
ID
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28

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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.: 8 / 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-5YK / 6-(2-fluoranylpyridin-4-yl)-~{N}-[(1~{R})-1-(3-methoxyphenyl)ethyl]pyridine-3-carboxamide


Mass: 351.374 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: C20H18FN3O2 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C3H8O3
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 77 / 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: 2.59 Å3/Da / Density % sol: 52.54 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 6.25 / 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: 0.99998 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: May 31, 2017
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.99998 Å / Relative weight: 1
ReflectionResolution: 2.75→98.79 Å / Num. obs: 88409 / % possible obs: 95.4 % / Redundancy: 1.7 % / Biso Wilson estimate: 64.445 Å2 / CC1/2: 0.998 / Rmerge(I) obs: 0.05 / Rrim(I) all: 0.07 / Χ2: 0.959 / Net I/σ(I): 12.24
Reflection shellResolution: 2.75→3 Å / Redundancy: 1.7 % / Rmerge(I) obs: 0.417 / Mean I/σ(I) obs: 1.92 / Num. unique obs: 302 / CC1/2: 0.999 / Rrim(I) all: 0.018 / % possible all: 95

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Processing

Software
NameVersionClassification
XSCALEdata scaling
REFMAC5.8.0155refinement
PDB_EXTRACT3.27data extraction
XDSdata reduction
MOLREPphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: NONE

Resolution: 2.75→98.79 Å / Cor.coef. Fo:Fc: 0.922 / Cor.coef. Fo:Fc free: 0.89 / SU B: 22.664 / SU ML: 0.415 / Cross valid method: THROUGHOUT / σ(F): 0 / ESU R Free: 0.421 / Stereochemistry target values: MAXIMUM LIKELIHOOD
Details: HYDROGENS HAVE BEEN ADDED IN THE RIDING POSITIONS U VALUES : REFINED INDIVIDUALLY
RfactorNum. reflection% reflectionSelection details
Rfree0.2865 700 0.8 %RANDOM
Rwork0.241 ---
obs0.2413 87709 95.53 %-
Solvent computationIon probe radii: 0.8 Å / Shrinkage radii: 0.8 Å / VDW probe radii: 1.2 Å / Solvent model: MASK
Displacement parametersBiso max: 184.12 Å2 / Biso mean: 66.701 Å2 / Biso min: 7.42 Å2
Baniso -1Baniso -2Baniso -3
1-2.07 Å2-0.47 Å21.67 Å2
2--0.19 Å2-3.78 Å2
3----1.3 Å2
Refinement stepCycle: final / Resolution: 2.75→98.79 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms24806 0 226 78 25110
Biso mean--53.87 43.45 -
Num. residues----3046
Refine LS restraints
Refine-IDTypeDev idealDev ideal targetNumber
X-RAY DIFFRACTIONr_bond_refined_d0.0110.01924709
X-RAY DIFFRACTIONr_bond_other_d0.0020.0222724
X-RAY DIFFRACTIONr_angle_refined_deg1.4151.95733527
X-RAY DIFFRACTIONr_angle_other_deg1.177351923
X-RAY DIFFRACTIONr_dihedral_angle_1_deg6.05353024
X-RAY DIFFRACTIONr_dihedral_angle_2_deg34.52923.9511154
X-RAY DIFFRACTIONr_dihedral_angle_3_deg13.339153857
X-RAY DIFFRACTIONr_dihedral_angle_4_deg16.28815133
X-RAY DIFFRACTIONr_chiral_restr0.0780.23597
X-RAY DIFFRACTIONr_gen_planes_refined0.0050.02128205
X-RAY DIFFRACTIONr_gen_planes_other0.0020.025916
Refine LS restraints NCS

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

Ens-IDDom-IDAuth asym-IDNumberRms dev position (Å)
11A225960.06
12B225960.06
21A228200.05
22C228200.05
31A234640.06
32D234640.06
41A229760.06
42E229760.06
51A230560.07
52F230560.07
61A231120.06
62G231120.06
71A220960.06
72H220960.06
81B221240.06
82C221240.06
91B225820.06
92D225820.06
101B222340.06
102E222340.06
111B224080.06
112F224080.06
121B224220.06
122G224220.06
131B215880.06
132H215880.06
141C228900.06
142D228900.06
151C222580.05
152E222580.05
161C224360.06
162F224360.06
171C224980.05
172G224980.05
181C217220.05
182H217220.05
191D228340.06
192E228340.06
201D233000.06
202F233000.06
211D231660.06
212G231660.06
221D221420.06
222H221420.06
231E224460.06
232F224460.06
241E225280.05
242G225280.05
251E216160.05
252H216160.05
261F226140.07
262G226140.07
271F216180.06
272H216180.06
281G217980.05
282H217980.05
LS refinement shellResolution: 2.75→2.821 Å / Rfactor Rfree error: 0 / Total num. of bins used: 20
RfactorNum. reflection% reflection
Rfree0.351 50 -
Rwork0.371 6491 -
all-6541 -
obs--94.65 %

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