[English] 日本語
Yorodumi
- PDB-4yve: ROCK 1 bound to methoxyphenyl thiazole inhibitor -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 4yve
TitleROCK 1 bound to methoxyphenyl thiazole inhibitor
ComponentsRho-associated protein kinase 1
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / kinase / dimer / dimerization / myosin / TRANSFERASE-TRANSFERASE INHIBITOR complex
Function / homology
Function and homology information


regulation of angiotensin-activated signaling pathway / apical constriction / podocyte cell migration / Rho-dependent protein serine/threonine kinase activity / positive regulation of phosphatase activity / regulation of keratinocyte differentiation / myoblast migration / positive regulation of connective tissue replacement / membrane to membrane docking / negative regulation of membrane protein ectodomain proteolysis ...regulation of angiotensin-activated signaling pathway / apical constriction / podocyte cell migration / Rho-dependent protein serine/threonine kinase activity / positive regulation of phosphatase activity / regulation of keratinocyte differentiation / myoblast migration / positive regulation of connective tissue replacement / membrane to membrane docking / negative regulation of membrane protein ectodomain proteolysis / response to transforming growth factor beta / : / regulation of cell junction assembly / positive regulation of dephosphorylation / negative regulation of bicellular tight junction assembly / bleb / negative regulation of phosphorylation / negative regulation of amyloid precursor protein catabolic process / neuron projection arborization / embryonic morphogenesis / bleb assembly / negative regulation of biomineral tissue development / leukocyte tethering or rolling / regulation of synapse maturation / positive regulation of amyloid-beta clearance / actomyosin structure organization / regulation of establishment of endothelial barrier / RHO GTPases Activate ROCKs / negative regulation of motor neuron apoptotic process / regulation of stress fiber assembly / regulation of cell motility / Sema4D induced cell migration and growth-cone collapse / response to angiotensin / aortic valve morphogenesis / regulation of establishment of cell polarity / RHOBTB1 GTPase cycle / motor neuron apoptotic process / RND3 GTPase cycle / regulation of synaptic vesicle endocytosis / regulation of neuron differentiation / cortical actin cytoskeleton organization / regulation of focal adhesion assembly / leukocyte cell-cell adhesion / leukocyte migration / RHOB GTPase cycle / tau-protein kinase activity / EPHA-mediated growth cone collapse / mRNA destabilization / positive regulation of cardiac muscle hypertrophy / Apoptotic cleavage of cellular proteins / RHOC GTPase cycle / negative regulation of amyloid-beta formation / positive regulation of focal adhesion assembly / mitotic cytokinesis / Rho protein signal transduction / RHOH GTPase cycle / smooth muscle contraction / epithelial to mesenchymal transition / RHOA GTPase cycle / regulation of cell adhesion / canonical NF-kappaB signal transduction / positive regulation of autophagy / regulation of microtubule cytoskeleton organization / ruffle / EPHB-mediated forward signaling / regulation of cell migration / centriole / negative regulation of angiogenesis / blood vessel diameter maintenance / negative regulation of protein binding / protein localization to plasma membrane / regulation of actin cytoskeleton organization / tau protein binding / Schaffer collateral - CA1 synapse / VEGFA-VEGFR2 Pathway / small GTPase binding / cytoplasmic stress granule / neuron projection development / G alpha (12/13) signalling events / lamellipodium / actin cytoskeleton organization / peptidyl-serine phosphorylation / secretory granule lumen / Potential therapeutics for SARS / positive regulation of MAPK cascade / cytoskeleton / non-specific serine/threonine protein kinase / protein kinase activity / protein phosphorylation / Golgi membrane / protein serine kinase activity / protein serine/threonine kinase activity / Neutrophil degranulation / positive regulation of gene expression / signal transduction / extracellular region / ATP binding / metal ion binding / plasma membrane / cytosol
Similarity search - Function
Rho-associated protein kinase 1, HR1 / 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 1, HR1 / 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 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / 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 / 2-Layer Sandwich / Orthogonal Bundle / Mainly Alpha / Alpha Beta
Similarity search - Domain/homology
Chem-4KK / Rho-associated protein kinase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / FOURIER SYNTHESIS / Resolution: 3.4 Å
AuthorsJacobs, M.D.
Citation
Journal: J.Med.Chem. / Year: 2015
Title: Design, Synthesis, and Structure-Activity Relationships of Pyridine-Based Rho Kinase (ROCK) Inhibitors.
Authors: Green, J. / Cao, J. / Bandarage, U.K. / Gao, H. / Court, J. / Marhefka, C. / Jacobs, M. / Taslimi, P. / Newsome, D. / Nakayama, T. / Shah, S. / Rodems, S.
#1: Journal: J. Biol. Chem. / Year: 2006
Title: The structure of dimeric ROCK I reveals the mechanism for ligand selectivity.
Authors: Jacobs, M. / Hayakawa, K. / Swenson, L. / Bellon, S. / Fleming, M. / Taslimi, P. / Doran, J.
#2: Journal: Bioorg. Med. Chem. Lett. / Year: 2018
Title: ROCK inhibitors 2. Improving potency, selectivity and solubility through the application of rationally designed solubilizing groups.
Authors: Gao, H. / Marhefka, C. / Jacobs, M.D. / Cao, J. / Bandarage, U.K. / Green, J.
History
DepositionMar 19, 2015Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 10, 2015Provider: repository / Type: Initial release
Revision 1.1Jun 17, 2015Group: Database references
Revision 1.2Jul 8, 2015Group: Data collection
Revision 1.3Jul 18, 2018Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Source and taxonomy
Category: citation / citation_author ...citation / citation_author / entity_src_gen / pdbx_struct_assembly / pdbx_struct_assembly_gen / pdbx_struct_assembly_prop / pdbx_struct_oper_list
Item: _entity_src_gen.pdbx_alt_source_flag / _pdbx_struct_assembly.oligomeric_details ..._entity_src_gen.pdbx_alt_source_flag / _pdbx_struct_assembly.oligomeric_details / _pdbx_struct_assembly_gen.asym_id_list / _pdbx_struct_assembly_prop.type / _pdbx_struct_assembly_prop.value / _pdbx_struct_oper_list.symmetry_operation
Revision 1.4Sep 27, 2023Group: Data collection / Database references / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model
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 1
B: Rho-associated protein kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)96,6754
Polymers96,0252
Non-polymers6512
Water1629
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area4290 Å2
ΔGint-30 kcal/mol
Surface area34870 Å2
MethodPISA
Unit cell
Length a, b, c (Å)181.980, 181.980, 90.560
Angle α, β, γ (deg.)90.000, 90.000, 120.000
Int Tables number152
Space group name H-MP3121

-
Components

#1: Protein Rho-associated protein kinase 1 / Renal carcinoma antigen NY-REN-35 / Rho-associated / coiled-coil-containing protein kinase 1 / ...Renal carcinoma antigen NY-REN-35 / Rho-associated / coiled-coil-containing protein kinase 1 / coiled-coil-containing protein kinase I / ROCK-I / p160 ROCK-1 / p160ROCK


Mass: 48012.285 Da / Num. of mol.: 2 / Fragment: N-terminal kinase domain (UNP residues 6-415)
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: ROCK1 / Plasmid: pBEV10 / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: Q13464, non-specific serine/threonine protein kinase
#2: Chemical ChemComp-4KK / 2-(3-methoxyphenyl)-N-[4-(pyridin-4-yl)-1,3-thiazol-2-yl]acetamide


Mass: 325.385 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C17H15N3O2S
#3: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 9 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 4.51 Å3/Da / Density % sol: 72.71 %
Crystal growTemperature: 298 K / Method: vapor diffusion, hanging drop / pH: 5.5
Details: 0.45 mM protein, 5% PEG3350, 100 mM MES, 50 mM calcium chloride, 10 mM DTT

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1.1 Å
DetectorType: ADSC QUANTUM 4 / Detector: CCD / Date: Jan 28, 2003
RadiationMonochromator: double crystal Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.1 Å / Relative weight: 1
ReflectionResolution: 3.4→29.78 Å / Num. obs: 23765 / % possible obs: 99 % / Redundancy: 7.41 % / Biso Wilson estimate: 94.4 Å2 / Rmerge(I) obs: 0.155 / Χ2: 2.29 / Net I/σ(I): 4.2 / Num. measured all: 178283 / Scaling rejects: 2109
Reflection shell

Diffraction-ID: 1

Resolution (Å)Redundancy (%)Rmerge(I) obsMean I/σ(I) obsNum. measured allNum. unique allΧ2Rejects% possible all
3.4-3.527.510.481.31798323941.326100
3.52-3.667.550.4071.61783123571.924499.7
3.66-3.837.540.3391.91800123752.58999.5
3.83-4.037.520.2932.21773923462.5410299.4
4.03-4.287.480.2282.81788123532.9326998.6
4.28-4.617.460.183.71794923523.2340898.1
4.61-5.077.430.1454.61789823502.5443697.8
5.07-5.87.440.1315.21776023562.1523898.7
5.8-7.297.340.1066.61786024271.784599.6
7.29-29.786.890.05612.21738124551.9947298

-
Processing

Software
NameVersionClassification
d*TREK7.1SSIdata reduction
d*TREK7.1SSIdata scaling
BUSTER-TNTBUSTER 2.11.6refinement
PDB_EXTRACT3.15data extraction
RefinementMethod to determine structure: FOURIER SYNTHESIS
Starting model: PDB entry 2ETR

2etr


Resolution: 3.4→19.86 Å / Cor.coef. Fo:Fc: 0.9051 / Cor.coef. Fo:Fc free: 0.8771 / Cross valid method: THROUGHOUT / σ(F): 0 / SU Rfree Blow DPI: 0.427
RfactorNum. reflection% reflectionSelection details
Rfree0.2443 1182 5.11 %RANDOM
Rwork0.2178 ---
obs0.2192 23114 96.65 %-
Displacement parametersBiso max: 184.88 Å2 / Biso mean: 85.88 Å2 / Biso min: 20 Å2
Baniso -1Baniso -2Baniso -3
1--7.726 Å20 Å20 Å2
2---7.726 Å20 Å2
3---15.4519 Å2
Refine analyzeLuzzati coordinate error obs: 0.728 Å
Refinement stepCycle: final / Resolution: 3.4→19.86 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms6365 0 46 9 6420
Biso mean--79.6 45.78 -
Num. residues----783
Refine LS restraints
Refine-IDTypeNumberRestraint functionWeightDev ideal
X-RAY DIFFRACTIONt_dihedral_angle_d2297SINUSOIDAL2
X-RAY DIFFRACTIONt_trig_c_planes174HARMONIC2
X-RAY DIFFRACTIONt_gen_planes942HARMONIC5
X-RAY DIFFRACTIONt_it6569HARMONIC20
X-RAY DIFFRACTIONt_nbd
X-RAY DIFFRACTIONt_improper_torsion
X-RAY DIFFRACTIONt_pseud_angle
X-RAY DIFFRACTIONt_chiral_improper_torsion802SEMIHARMONIC5
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_contact7776SEMIHARMONIC4
X-RAY DIFFRACTIONt_bond_d6569HARMONIC20.01
X-RAY DIFFRACTIONt_angle_deg8873HARMONIC21.13
X-RAY DIFFRACTIONt_omega_torsion2.75
X-RAY DIFFRACTIONt_other_torsion21.7
LS refinement shellResolution: 3.4→3.55 Å / Total num. of bins used: 12
RfactorNum. reflection% reflection
Rfree0.3326 142 5.06 %
Rwork0.2598 2665 -
all0.2634 2807 -
obs--96.65 %
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL11 (°2)L12 (°2)L13 (°2)L22 (°2)L23 (°2)L33 (°2)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T11 (Å2)T12 (Å2)T13 (Å2)T22 (Å2)T23 (Å2)T33 (Å2)Origin x (Å)Origin y (Å)Origin z (Å)
15.1974-1.75310.24011.8035-1.37012.87440.003-0.4737-0.23870.07010.30830.2741-0.0479-0.3235-0.3113-0.05530.16260.11740.1079-0.0113-0.291125.4692117.645327.8067
26.1899-1.10290.64570.7421-0.94120.0068-0.0835-0.7221-0.56220.27310.2238-0.0176-0.1722-0.3954-0.1402-0.03630.16820.06940.12040.1838-0.178242.8875104.63828.3673
33.20350.21610.45912.1540.92453.81110.05010.01050.2129-0.21850.1041-0.4891-0.45020.361-0.1542-0.05150.13870.0486-0.10090.0135-0.132568.2882109.331426.3199
43.88221.60030.88640.697-0.45770.8922-0.0557-0.5361-0.38110.3893-0.0512-0.1554-0.096-0.43610.10690.00240.2217-0.01380.09740.1629-0.249840.2441105.172630.8101
53.691-2.9006-0.88583.10711.58151.6132-0.0213-0.5213-0.00520.15130.1446-0.0223-0.27530.1733-0.1233-0.07730.12180.10980.1330.044-0.275126.3366123.07526.5264
65.9531-1.72880.8131.228-0.45180-0.0884-0.46850.61990.14280.2605-0.10250.02870.4074-0.17210.01850.2640.11080.0647-0.1115-0.20588.5983134.478921.245
73.5398-0.4152-1.08883.8026-0.54874.4558-0.04450.0318-0.49890.00920.00160.24310.610.02850.04290.15980.145-0.0295-0.2911-0.023-0.032-15.6889126.227921.0516
83.8780.16352.75421.2214-0.6117.3026-0.1519-0.27380.4690.22810.2610.14790.09850.5629-0.1091-0.0050.27120.16530.0328-0.0538-0.296410.4802136.321825.6397
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection detailsAuth asym-IDAuth seq-ID
1X-RAY DIFFRACTION1{A|1 - 71}A1 - 71
2X-RAY DIFFRACTION2{A|72 - 157}A72 - 157
3X-RAY DIFFRACTION3{A|158 - 356}A158 - 356
4X-RAY DIFFRACTION4{A|357 - 405}A357 - 405
5X-RAY DIFFRACTION5{B|1 - 71}B1 - 71
6X-RAY DIFFRACTION6{B|72 - 157}B72 - 157
7X-RAY DIFFRACTION7{B|158 - 356}B158 - 356
8X-RAY DIFFRACTION8{B|357 - 402}B357 - 402

+
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