[English] 日本語
Yorodumi
- PDB-5dew: Crystal structure of PAK1 in complex with an inhibitor compound 5 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5dew
TitleCrystal structure of PAK1 in complex with an inhibitor compound 5
ComponentsSerine/threonine-protein kinase PAK 1
KeywordsTRANSFERASE/TRANSFERASE INHIBITOR / transferase-transferase inhibitor complex
Function / homology
Function and homology information


negative regulation of cell proliferation involved in contact inhibition / protein localization to cytoplasmic stress granule / positive regulation of microtubule nucleation / hepatocyte growth factor receptor signaling pathway / RHO GTPases Activate ROCKs / gamma-tubulin binding / Activation of RAC1 / CD28 dependent Vav1 pathway / Ephrin signaling / positive regulation of intracellular estrogen receptor signaling pathway ...negative regulation of cell proliferation involved in contact inhibition / protein localization to cytoplasmic stress granule / positive regulation of microtubule nucleation / hepatocyte growth factor receptor signaling pathway / RHO GTPases Activate ROCKs / gamma-tubulin binding / Activation of RAC1 / CD28 dependent Vav1 pathway / Ephrin signaling / positive regulation of intracellular estrogen receptor signaling pathway / DSCAM interactions / RHOV GTPase cycle / regulation of axonogenesis / branching morphogenesis of an epithelial tube / Fc-gamma receptor signaling pathway involved in phagocytosis / RHOJ GTPase cycle / RHOQ GTPase cycle / exocytosis / RHO GTPases activate PAKs / stimulatory C-type lectin receptor signaling pathway / regulation of MAPK cascade / RHOH GTPase cycle / CDC42 GTPase cycle / RHOU GTPase cycle / Sema3A PAK dependent Axon repulsion / Generation of second messenger molecules / intercalated disc / Smooth Muscle Contraction / RAC3 GTPase cycle / RAC2 GTPase cycle / ephrin receptor signaling pathway / localization / positive regulation of microtubule polymerization / RHO GTPases activate PKNs / positive regulation of JUN kinase activity / positive regulation of stress fiber assembly / ruffle / RAC1 GTPase cycle / EPHB-mediated forward signaling / collagen binding / CD209 (DC-SIGN) signaling / neuron projection morphogenesis / VEGFR2 mediated vascular permeability / Signal transduction by L1 / actin filament / regulation of actin cytoskeleton organization / FCERI mediated MAPK activation / MAPK6/MAPK4 signaling / wound healing / G beta:gamma signalling through CDC42 / Regulation of actin dynamics for phagocytic cup formation / ruffle membrane / Z disc / cell-cell junction / cell migration / lamellipodium / positive regulation of peptidyl-serine phosphorylation / chromosome / actin cytoskeleton organization / nuclear membrane / protein autophosphorylation / non-specific serine/threonine protein kinase / protein kinase activity / positive regulation of cell migration / intracellular signal transduction / chromatin remodeling / positive regulation of protein phosphorylation / axon / phosphorylation / protein phosphorylation / focal adhesion / protein serine kinase activity / protein serine/threonine kinase activity / centrosome / dendrite / apoptotic process / DNA damage response / positive regulation of cell population proliferation / protein-containing complex / nucleoplasm / ATP binding / identical protein binding / plasma membrane / cytosol / cytoplasm
Similarity search - Function
p21 activated kinase binding domain / CRIB domain superfamily / P21-Rho-binding domain / CRIB domain profile. / P21-Rho-binding domain / CRIB domain / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 ...p21 activated kinase binding domain / CRIB domain superfamily / P21-Rho-binding domain / CRIB domain profile. / P21-Rho-binding domain / CRIB domain / 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-59N / Serine/threonine-protein kinase PAK 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / Resolution: 1.9 Å
AuthorsOh, A. / Tam, C. / Wang, W.
CitationJournal: To Be Published
Title: Design of Selective PAK1 Inhibitor G-5555: Improving Proper-ties by Employing an Unorthodox Low-pKa Polar Moiety
Authors: Ndubaku, C.O.
History
DepositionAug 26, 2015Deposition site: RCSB / Processing site: RCSB
Revision 1.0Sep 21, 2016Provider: repository / Type: Initial release
Revision 1.1Mar 6, 2024Group: Data collection / Database references / Derived calculations
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_struct_oper_list
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession / _pdbx_struct_oper_list.symmetry_operation

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: Serine/threonine-protein kinase PAK 1
B: Serine/threonine-protein kinase PAK 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)67,5814
Polymers66,5732
Non-polymers1,0082
Water8,161453
1
A: Serine/threonine-protein kinase PAK 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,7902
Polymers33,2861
Non-polymers5041
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
2
B: Serine/threonine-protein kinase PAK 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,7902
Polymers33,2861
Non-polymers5041
Water181
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)62.556, 81.053, 66.499
Angle α, β, γ (deg.)90.00, 106.39, 90.00
Int Tables number4
Space group name H-MP1211

-
Components

#1: Protein Serine/threonine-protein kinase PAK 1 / Alpha-PAK / p21-activated kinase 1 / PAK-1 / p65-PAK


Mass: 33286.270 Da / Num. of mol.: 2 / Fragment: Protein kinase domain residue 249-545 / Mutation: D389N, T423E
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PAK1 / Production host: Escherichia coli (E. coli)
References: UniProt: Q13153, non-specific serine/threonine protein kinase
#2: Chemical ChemComp-59N / 8-[(trans-4-aminocyclohexyl)methyl]-6-[2-chloro-4-(6-methylpyrazin-2-yl)phenyl]-2-(ethylamino)pyrido[2,3-d]pyrimidin-7(8H)-one


Mass: 504.026 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: C27H30ClN7O
#3: Water ChemComp-HOH / water / Water


Mass: 18.015 Da / Num. of mol.: 453 / Source method: isolated from a natural source / Formula: H2O

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION

-
Sample preparation

CrystalDensity Matthews: 2.43 Å3/Da / Density % sol: 49.37 %
Crystal growTemperature: 292 K / Method: vapor diffusion, sitting drop / pH: 7
Details: crystals were grown at 19 C from 1.0 uL + 1.0 uL vapor diffusion drops containing 10 mg/mL protein, 1 mM ligand, 0.15 M DL-Malic Acid pH 7.0, 20% - 30% PEG 3350, 4% 1,3-Propanediol and 0.1 M ...Details: crystals were grown at 19 C from 1.0 uL + 1.0 uL vapor diffusion drops containing 10 mg/mL protein, 1 mM ligand, 0.15 M DL-Malic Acid pH 7.0, 20% - 30% PEG 3350, 4% 1,3-Propanediol and 0.1 M Sodium Malonate, VAPOR DIFFUSION, SITTING DROP, temperature 292K

-
Data collection

DiffractionMean temperature: 93 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.2 / Wavelength: 1.00004 Å
DetectorType: ADSC QUANTUM 315 / Detector: CCD / Date: May 15, 2013
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.00004 Å / Relative weight: 1
ReflectionResolution: 1.9→50 Å / Num. obs: 13786 / % possible obs: 99.9 % / Redundancy: 3.7 % / Net I/σ(I): 17.8

-
Processing

Software
NameVersionClassification
PHENIX1.9_1692refinement
HKL-2000data reduction
SCALEPACKdata scaling
PHASERphasing
RefinementResolution: 1.9→48.231 Å / SU ML: 0.18 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 22.73 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2153 2590 5.08 %
Rwork0.1749 --
obs0.177 50952 99.1 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 1.9→48.231 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms4494 0 72 453 5019
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0074648
X-RAY DIFFRACTIONf_angle_d1.1446291
X-RAY DIFFRACTIONf_dihedral_angle_d13.8431751
X-RAY DIFFRACTIONf_chiral_restr0.044714
X-RAY DIFFRACTIONf_plane_restr0.005807
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.8854-1.91960.32921210.26112153X-RAY DIFFRACTION85
1.9196-1.95660.2611350.22922556X-RAY DIFFRACTION100
1.9566-1.99650.23051250.22092542X-RAY DIFFRACTION100
1.9965-2.03990.23261290.20942576X-RAY DIFFRACTION100
2.0399-2.08740.22491400.19652572X-RAY DIFFRACTION100
2.0874-2.13960.231220.18872546X-RAY DIFFRACTION100
2.1396-2.19740.21111430.17652560X-RAY DIFFRACTION100
2.1974-2.26210.22321510.18242531X-RAY DIFFRACTION100
2.2621-2.33510.20191320.17812563X-RAY DIFFRACTION100
2.3351-2.41850.23231440.17152549X-RAY DIFFRACTION100
2.4185-2.51540.25391280.1842568X-RAY DIFFRACTION100
2.5154-2.62980.24291280.18242590X-RAY DIFFRACTION100
2.6298-2.76850.21621500.18442558X-RAY DIFFRACTION100
2.7685-2.94190.21041450.18952536X-RAY DIFFRACTION100
2.9419-3.1690.24421540.19132575X-RAY DIFFRACTION100
3.169-3.48780.23831230.18142597X-RAY DIFFRACTION100
3.4878-3.99230.1951410.16112574X-RAY DIFFRACTION100
3.9923-5.02910.16921470.13852567X-RAY DIFFRACTION100
5.0291-48.2470.20161320.15472649X-RAY DIFFRACTION100
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)
10.5961-0.089-0.17940.49010.04580.39870.05220.2501-0.062-0.10010.0044-0.00660.031-0.2193-00.29330.09280.03560.31920.00710.201922.3941-21.60986.9482
20.5765-0.2663-0.51740.66920.27592.3284-0.0152-0.0288-0.0362-0.052-0.0301-0.0063-0.12750.36520.00020.10550.0051-0.01950.15490.00560.097724.1990.258521.2673
30.17290.25790.06490.4250.25570.32630.04850.00340.05370.3405-0.00880.34870.2181-0.13100.2624-0.05790.07780.1787-0.01580.3189-2.3899-15.1196-15.2712
40.72210.2197-0.140.2942-0.05910.9883-0.0341-0.07360.03310.11480.0190.07820.0202-0.0161-00.13530.02060.00150.1183-0.02580.163114.9195.7117-17.1409
Refinement TLS group
IDRefine-IDRefine TLS-IDSelection details
1X-RAY DIFFRACTION1chain A and resid 250:346
2X-RAY DIFFRACTION2chain A and resid 347:541 or chain A and resid 601
3X-RAY DIFFRACTION3chain B and resid 255:346
4X-RAY DIFFRACTION4chain B and resid 347:541 or chain B and resid 601

+
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