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

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 5dfp
TitleCrystal structure of PAK1 in complex with an inhibitor compound FRAX1036
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 / Ephrin signaling / CD28 dependent Vav1 pathway / regulation of axonogenesis ...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 / Ephrin signaling / CD28 dependent Vav1 pathway / regulation of axonogenesis / phosphorylation / RHOV GTPase cycle / branching morphogenesis of an epithelial tube / positive regulation of intracellular estrogen receptor signaling pathway / RHOJ GTPase cycle / stimulatory C-type lectin receptor signaling pathway / RHOQ GTPase cycle / exocytosis / RHO GTPases activate PAKs / Fc-gamma receptor signaling pathway involved in phagocytosis / regulation of MAPK cascade / RHOU GTPase cycle / CDC42 GTPase cycle / RHOH GTPase cycle / Generation of second messenger molecules / positive regulation of JUN kinase activity / Sema3A PAK dependent Axon repulsion / intercalated disc / ephrin receptor signaling pathway / Smooth Muscle Contraction / RAC2 GTPase cycle / RAC3 GTPase cycle / RHO GTPases activate PKNs / positive regulation of peptidyl-serine phosphorylation / collagen binding / positive regulation of stress fiber assembly / ruffle / positive regulation of microtubule polymerization / EPHB-mediated forward signaling / RAC1 GTPase cycle / CD209 (DC-SIGN) signaling / neuron projection morphogenesis / cellular response to starvation / Signal transduction by L1 / VEGFR2 mediated vascular permeability / actin filament / regulation of actin cytoskeleton organization / FCERI mediated MAPK activation / wound healing / MAPK6/MAPK4 signaling / Regulation of actin dynamics for phagocytic cup formation / Z disc / ruffle membrane / G beta:gamma signalling through CDC42 / cell-cell junction / cell migration / lamellipodium / positive regulation of protein phosphorylation / chromosome / actin cytoskeleton organization / protein autophosphorylation / nuclear membrane / eukaryotic translation initiation factor 2alpha kinase activity / 3-phosphoinositide-dependent protein kinase activity / DNA-dependent protein kinase activity / ribosomal protein S6 kinase activity / histone H3S10 kinase activity / histone H2AXS139 kinase activity / histone H3S28 kinase activity / histone H4S1 kinase activity / histone H2BS14 kinase activity / histone H3T3 kinase activity / histone H2AS121 kinase activity / Rho-dependent protein serine/threonine kinase activity / histone H2BS36 kinase activity / histone H3S57 kinase activity / histone H2AT120 kinase activity / AMP-activated protein kinase activity / histone H2AS1 kinase activity / histone H3T6 kinase activity / histone H3T11 kinase activity / histone H3T45 kinase activity / non-specific serine/threonine protein kinase / protein kinase activity / intracellular signal transduction / positive regulation of cell migration / protein phosphorylation / chromatin remodeling / axon / protein serine kinase activity / focal adhesion / protein serine/threonine kinase activity / apoptotic process / positive regulation of cell population proliferation / centrosome / dendrite / DNA damage response / protein-containing complex / nucleoplasm / ATP binding
Similarity search - Function
p21 activated kinase binding domain / : / CRIB domain superfamily / P21-Rho-binding domain / CRIB domain profile. / P21-Rho-binding domain / CRIB domain / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 ...p21 activated kinase binding domain / : / CRIB domain superfamily / P21-Rho-binding domain / CRIB domain profile. / P21-Rho-binding domain / CRIB domain / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); 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-59U / Serine/threonine-protein kinase PAK 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / Resolution: 2.2 Å
AuthorsMaksimoska, J. / Marmorstein, R. / Wang, W.
CitationJournal: Acs Med.Chem.Lett. / Year: 2015
Title: Design of Selective PAK1 Inhibitor G-5555: Improving Properties by Employing an Unorthodox Low-pK a Polar Moiety.
Authors: Ndubaku, C.O. / Crawford, J.J. / Drobnick, J. / Aliagas, I. / Campbell, D. / Dong, P. / Dornan, L.M. / Duron, S. / Epler, J. / Gazzard, L. / Heise, C.E. / Hoeflich, K.P. / Jakubiak, D. / La, ...Authors: Ndubaku, C.O. / Crawford, J.J. / Drobnick, J. / Aliagas, I. / Campbell, D. / Dong, P. / Dornan, L.M. / Duron, S. / Epler, J. / Gazzard, L. / Heise, C.E. / Hoeflich, K.P. / Jakubiak, D. / La, H. / Lee, W. / Lin, B. / Lyssikatos, J.P. / Maksimoska, J. / Marmorstein, R. / Murray, L.J. / O'Brien, T. / Oh, A. / Ramaswamy, S. / Wang, W. / Zhao, X. / Zhong, Y. / Blackwood, E. / Rudolph, J.
History
DepositionAug 27, 2015Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jan 27, 2016Provider: repository / Type: Initial release
Revision 1.1Oct 23, 2024Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Structure summary
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_entry_details / pdbx_modification_feature / 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
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,9633
Polymers33,3671
Non-polymers5962
Water3,657203
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPISA
Unit cell
Length a, b, c (Å)51.965, 103.819, 123.542
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number20
Space group name H-MC2221
Components on special symmetry positions
IDModelComponents
11A-727-

HOH

-
Components

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


Mass: 33367.242 Da / Num. of mol.: 1 / Fragment: Protein kinase domain residue 249-545 / Mutation: K299R
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-59U / 6-[2-chloro-4-(6-methylpyrazin-2-yl)phenyl]-8-ethyl-2-{[2-(1-methylpiperidin-4-yl)ethyl]amino}pyrido[2,3-d]pyrimidin-7(8H)-one


Mass: 518.053 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C28H32ClN7O
#3: Chemical ChemComp-DMS / DIMETHYL SULFOXIDE


Mass: 78.133 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H6OS / Comment: DMSO, precipitant*YM
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 203 / Source method: isolated from a natural source / Formula: H2O
Has protein modificationY

-
Experimental details

-
Experiment

ExperimentMethod: X-RAY DIFFRACTION

-
Sample preparation

CrystalDensity Matthews: 2.5 Å3/Da / Density % sol: 50.74 %
Crystal growTemperature: 277 K / Method: vapor diffusion, hanging drop / pH: 7
Details: 1 uL of PAK1 (9 mg/ml) with 1 uL of crystallization solution (0.1 M HEPES pH 7.0, 1 M NaCl, 25% PEG 3350, 10 mM DTT) at 4C

-
Data collection

DiffractionMean temperature: 93 K
Diffraction sourceSource: ROTATING ANODE / Type: RIGAKU MICROMAX-007 HF / Wavelength: 1.54 Å
DetectorType: RIGAKU SATURN 944+ / Detector: CCD / Date: Jun 12, 2009
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1.54 Å / Relative weight: 1
ReflectionResolution: 2.2→50 Å / Num. obs: 17366 / % possible obs: 99.5 % / Redundancy: 4.8 % / Net I/σ(I): 10.1

-
Processing

Software
NameVersionClassification
PHENIX1.8_1069refinement
HKL-2000data reduction
SCALEPACKdata scaling
PHASERphasing
RefinementResolution: 2.2→30.82 Å / SU ML: 0.27 / Cross valid method: FREE R-VALUE / σ(F): 1.34 / Phase error: 25.84 / Stereochemistry target values: ML
RfactorNum. reflection% reflection
Rfree0.2464 865 5 %
Rwork0.1903 --
obs0.1931 17297 99.2 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Refinement stepCycle: LAST / Resolution: 2.2→30.82 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2275 0 41 203 2519
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.0082361
X-RAY DIFFRACTIONf_angle_d1.1363202
X-RAY DIFFRACTIONf_dihedral_angle_d15.653897
X-RAY DIFFRACTIONf_chiral_restr0.071365
X-RAY DIFFRACTIONf_plane_restr0.004406
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.1976-2.33520.32771410.24052664X-RAY DIFFRACTION98
2.3352-2.51540.28971430.22772701X-RAY DIFFRACTION99
2.5154-2.76840.2711440.22762734X-RAY DIFFRACTION100
2.7684-3.16870.27941440.22542726X-RAY DIFFRACTION100
3.1687-3.99080.22141460.15732762X-RAY DIFFRACTION100
3.9908-30.8230.20811470.16562845X-RAY DIFFRACTION98

+
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