[English] 日本語
Yorodumi
- PDB-7jnt: CRYSTAL STRUCTURE OF RHO-ASSOCIATED PROTEIN KINASE 2 (ROCK2) IN C... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7jnt
TitleCRYSTAL STRUCTURE OF RHO-ASSOCIATED PROTEIN KINASE 2 (ROCK2) IN COMPLEX WITH A POTENT AND SELECTIVE DUAL ROCK INHIBITOR
ComponentsRho-associated protein kinase 2
KeywordsTRANSFERASE / ROCK 2 / KINASE / TRANSFERASE-TRANSFERASE INHIBIT COMPLEX / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


cellular response to acetylcholine / positive regulation of connective tissue growth factor production / positive regulation of amyloid precursor protein catabolic process / positive regulation of centrosome duplication / regulation of angiotensin-activated signaling pathway / Rho-dependent protein serine/threonine kinase activity / negative regulation of protein localization to lysosome / regulation of keratinocyte differentiation / positive regulation of connective tissue replacement / positive regulation of fibroblast growth factor production ...cellular response to acetylcholine / positive regulation of connective tissue growth factor production / positive regulation of amyloid precursor protein catabolic process / positive regulation of centrosome duplication / regulation of angiotensin-activated signaling pathway / Rho-dependent protein serine/threonine kinase activity / negative regulation of protein localization to lysosome / regulation of keratinocyte differentiation / positive regulation of connective tissue replacement / positive regulation of fibroblast growth factor production / positive regulation of aspartic-type endopeptidase activity involved in amyloid precursor protein catabolic process / response to transforming growth factor beta / negative regulation of myosin-light-chain-phosphatase activity / regulation of nervous system process / regulation of cell junction assembly / negative regulation of bicellular tight junction assembly / regulation of protein metabolic process / modulation by host of viral process / regulation of cellular response to hypoxia / positive regulation of protein localization to early endosome / embryonic morphogenesis / negative regulation of nitric oxide biosynthetic process / negative regulation of biomineral tissue development / cellular response to testosterone stimulus / actomyosin structure organization / regulation of establishment of endothelial barrier / RHO GTPases Activate ROCKs / regulation of stress fiber assembly / regulation of cell motility / Sema4D induced cell migration and growth-cone collapse / aortic valve morphogenesis / response to angiotensin / regulation of establishment of cell polarity / RHOBTB1 GTPase cycle / cortical actin cytoskeleton organization / regulation of focal adhesion assembly / RHOB GTPase cycle / positive regulation of amyloid-beta formation / tau-protein kinase activity / EPHA-mediated growth cone collapse / mRNA destabilization / positive regulation of cardiac muscle hypertrophy / RHOC GTPase cycle / RHOH GTPase cycle / centrosome duplication / mitotic cytokinesis / Rho protein signal transduction / smooth muscle contraction / RHOA GTPase cycle / epithelial to mesenchymal transition / canonical NF-kappaB signal transduction / regulation of cell adhesion / positive regulation of stress fiber assembly / EPHB-mediated forward signaling / blood vessel diameter maintenance / negative regulation of angiogenesis / positive regulation of endothelial cell migration / response to ischemia / protein localization to plasma membrane / regulation of actin cytoskeleton organization / peptidyl-threonine phosphorylation / tau protein binding / regulation of circadian rhythm / cytoplasmic ribonucleoprotein granule / small GTPase binding / VEGFA-VEGFR2 Pathway / rhythmic process / G alpha (12/13) signalling events / actin cytoskeleton organization / peptidyl-serine phosphorylation / Potential therapeutics for SARS / positive regulation of MAPK cascade / cytoskeleton / non-specific serine/threonine protein kinase / positive regulation of cell migration / positive regulation of protein phosphorylation / negative regulation of gene expression / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / centrosome / positive regulation of gene expression / structural molecule activity / RNA binding / ATP binding / metal ion 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. / 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) ...: / Rho-associated protein kinase 2, HR1 domain / ROCK, Rho binding domain / Rho-associated protein kinase 1/2 / Rho Binding / Rho-binding (RhoBD) domain profile. / 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
Chem-VFA / Rho-associated protein kinase 2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.214 Å
AuthorsMuckelbauer, J.K.
CitationJournal: Bioorg.Med.Chem.Lett. / Year: 2020
Title: Identification of 5H-chromeno[3,4-c]pyridine and 6H-isochromeno[3,4-c]pyridine derivatives as potent and selective dual ROCK inhibitors.
Authors: Hu, Z. / Wang, C. / Sitkoff, D. / Cheadle, N.L. / Xu, S. / Muckelbauer, J.K. / Adam, L.P. / Wexler, R.R. / Quan, M.L.
History
DepositionAug 5, 2020Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 2, 2020Provider: repository / Type: Initial release
Revision 1.1Mar 6, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
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)369,65625
Polymers365,6078
Non-polymers4,04917
Water4,918273
1
A: Rho-associated protein kinase 2
B: Rho-associated protein kinase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)92,3256
Polymers91,4022
Non-polymers9234
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3400 Å2
ΔGint-26 kcal/mol
Surface area32990 Å2
MethodPISA
2
C: Rho-associated protein kinase 2
D: Rho-associated protein kinase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)92,3256
Polymers91,4022
Non-polymers9234
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3390 Å2
ΔGint-26 kcal/mol
Surface area33270 Å2
MethodPISA
3
E: Rho-associated protein kinase 2
F: Rho-associated protein kinase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)92,5217
Polymers91,4022
Non-polymers1,1195
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3360 Å2
ΔGint-26 kcal/mol
Surface area33590 Å2
MethodPISA
4
G: Rho-associated protein kinase 2
H: Rho-associated protein kinase 2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)92,4856
Polymers91,4022
Non-polymers1,0834
Water362
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area3390 Å2
ΔGint-25 kcal/mol
Surface area34210 Å2
MethodPISA
Unit cell
Length a, b, c (Å)93.617, 100.992, 102.888
Angle α, β, γ (deg.)83.11, 73.53, 78.38
Int Tables number1
Space group name H-MP1

-
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
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ROCK2, KIAA0619 / Production host: Trichoplusia ni (cabbage looper)
References: UniProt: O75116, non-specific serine/threonine protein kinase
#2: Chemical
ChemComp-VFA / N-[(3-methoxyphenyl)methyl]-5H-[1]benzopyrano[3,4-c]pyridine-8-carboxamide


Mass: 346.379 Da / Num. of mol.: 8 / Source method: obtained synthetically / Formula: C21H18N2O3 / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical
ChemComp-MES / 2-(N-MORPHOLINO)-ETHANESULFONIC ACID / MES (buffer)


Mass: 195.237 Da / Num. of mol.: 6 / Source method: obtained synthetically / Formula: C6H13NO4S / Comment: pH buffer*YM
#4: Chemical ChemComp-CL / CHLORIDE ION / Chloride


Mass: 35.453 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: Cl
#5: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 273 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.49 Å3/Da / Density % sol: 50.6 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / Details: NULL

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X06DA / Wavelength: 1 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Mar 1, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.21→98.7 Å / Num. obs: 105798 / % possible obs: 60.1 % / Observed criterion σ(I): 0 / Redundancy: 2.2 % / Biso Wilson estimate: 61.57 Å2 / Rmerge(I) obs: 0.037 / Net I/σ(I): 11.3
Reflection shellResolution: 2.21→2.46 Å / Redundancy: 2.4 % / Rmerge(I) obs: 0.546 / Mean I/σ(I) obs: 1.6 / Num. unique obs: 5290 / % possible all: 11.2

-
Processing

Software
NameVersionClassification
BUSTER2.11.7 (6-FEB-2020)refinement
XDSdata reduction
Aimlessdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: NULL

Resolution: 2.214→98.44 Å / Cor.coef. Fo:Fc: 0.933 / Cor.coef. Fo:Fc free: 0.915 / SU R Cruickshank DPI: 0.953 / Cross valid method: THROUGHOUT / σ(F): 0 / SU R Blow DPI: 0.713 / SU Rfree Blow DPI: 0.299 / SU Rfree Cruickshank DPI: 0.312
RfactorNum. reflection% reflectionSelection details
Rfree0.2488 865 0.82 %RANDOM
Rwork0.2112 ---
obs0.2115 105798 60.1 %-
Displacement parametersBiso mean: 56.75 Å2
Baniso -1Baniso -2Baniso -3
1--0.7978 Å2-0.169 Å20.3416 Å2
2--0.2033 Å2-0.6212 Å2
3---0.5945 Å2
Refine analyzeLuzzati coordinate error obs: 0.37 Å
Refinement stepCycle: LAST / Resolution: 2.214→98.44 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms23623 0 283 285 24191
Refine LS restraints
Refine-IDTypeDev idealNumberRestraint functionWeight
X-RAY DIFFRACTIONt_bond_d0.00824751HARMONIC2
X-RAY DIFFRACTIONt_angle_deg0.933650HARMONIC2
X-RAY DIFFRACTIONt_dihedral_angle_d8174SINUSOIDAL2
X-RAY DIFFRACTIONt_incorr_chiral_ct
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_trig_c_planes
X-RAY DIFFRACTIONt_gen_planes4590HARMONIC5
X-RAY DIFFRACTIONt_it24751HARMONIC10
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_omega_torsion2.95
X-RAY DIFFRACTIONt_other_torsion17.84
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_chiral_improper_torsion3095SEMIHARMONIC5
X-RAY DIFFRACTIONt_sum_occupancies
X-RAY DIFFRACTIONt_utility_distance
X-RAY DIFFRACTIONt_utility_angle
X-RAY DIFFRACTIONt_utility_torsion
X-RAY DIFFRACTIONt_ideal_dist_contact17455SEMIHARMONIC4
LS refinement shellResolution: 2.214→2.38 Å
RfactorNum. reflection% reflection
Rfree0.2848 -0.73 %
Rwork0.2238 2443 -
obs--7.18 %

+
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