[English] 日本語
Yorodumi
- PDB-2pe1: CRYSTAL STRUCTURE OF HUMAN PHOSPHOINOSITIDE-DEPENDENT PROTEIN KIN... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2pe1
TitleCRYSTAL STRUCTURE OF HUMAN PHOSPHOINOSITIDE-DEPENDENT PROTEIN KINASE 1 (PDK1) {2-Oxo-3-[1-(1H-pyrrol-2-yl)-eth-(Z)-ylidene]-2,3-dihydro-1H-indol-5-yl}-urea {BX-517} COMPLEX
Components3-phosphoinositide-dependent protein kinase 1
KeywordsTRANSFERASE / PROTEIN INHIBITOR COMPLEX / SERINE KINASE
Function / homology
Function and homology information


3-phosphoinositide-dependent protein kinase activity / Activation of AKT2 / regulation of mast cell degranulation / negative regulation of toll-like receptor signaling pathway / type B pancreatic cell development / positive regulation of phospholipase activity / RSK activation / hyperosmotic response / regulation of canonical NF-kappaB signal transduction / negative regulation of cardiac muscle cell apoptotic process ...3-phosphoinositide-dependent protein kinase activity / Activation of AKT2 / regulation of mast cell degranulation / negative regulation of toll-like receptor signaling pathway / type B pancreatic cell development / positive regulation of phospholipase activity / RSK activation / hyperosmotic response / regulation of canonical NF-kappaB signal transduction / negative regulation of cardiac muscle cell apoptotic process / positive regulation of vascular endothelial cell proliferation / phospholipase activator activity / positive regulation of sprouting angiogenesis / Constitutive Signaling by AKT1 E17K in Cancer / phospholipase binding / CD28 dependent PI3K/Akt signaling / positive regulation of blood vessel endothelial cell migration / Role of LAT2/NTAL/LAB on calcium mobilization / Estrogen-stimulated signaling through PRKCZ / SARS-CoV-2 targets host intracellular signalling and regulatory pathways / negative regulation of endothelial cell apoptotic process / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / extrinsic apoptotic signaling pathway / RHO GTPases activate PKNs / cellular response to epidermal growth factor stimulus / GPVI-mediated activation cascade / T cell costimulation / activation of protein kinase B activity / Integrin signaling / positive regulation of release of sequestered calcium ion into cytosol / insulin-like growth factor receptor signaling pathway / VEGFR2 mediated vascular permeability / VEGFR2 mediated cell proliferation / cell projection / calcium-mediated signaling / positive regulation of protein localization to plasma membrane / negative regulation of transforming growth factor beta receptor signaling pathway / peptidyl-threonine phosphorylation / negative regulation of protein kinase activity / epidermal growth factor receptor signaling pathway / CLEC7A (Dectin-1) signaling / FCERI mediated NF-kB activation / G beta:gamma signalling through PI3Kgamma / cellular response to insulin stimulus / positive regulation of angiogenesis / cell migration / Regulation of TP53 Degradation / Downstream TCR signaling / PIP3 activates AKT signaling / insulin receptor signaling pathway / cytoplasmic vesicle / actin cytoskeleton organization / postsynaptic density / protein autophosphorylation / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / non-specific serine/threonine protein kinase / intracellular signal transduction / protein phosphorylation / focal adhesion / protein serine kinase activity / protein serine/threonine kinase activity / ATP binding / nucleus / plasma membrane / cytosol / cytoplasm
Similarity search - Function
PDK1-type, PH domain / PDPK1 family / PH 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. ...PDK1-type, PH domain / PDPK1 family / PH 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-517 / 3-phosphoinositide-dependent protein kinase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / DIFFERENCE FOURIER PLUS REFINEMENT / Resolution: 2.14 Å
AuthorsWhitlow, M. / Adler, M.
Citation
Journal: Bioorg.Med.Chem.Lett. / Year: 2007
Title: Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 1: Design, synthesis and biological activity.
Authors: Islam, I. / Bryant, J. / Chou, Y.L. / Kochanny, M.J. / Lee, W. / Phillips, G.B. / Yu, H. / Adler, M. / Whitlow, M. / Ho, E. / Lentz, D. / Polokoff, M.A. / Subramanyam, B. / Wu, J.M. / Zhu, D. ...Authors: Islam, I. / Bryant, J. / Chou, Y.L. / Kochanny, M.J. / Lee, W. / Phillips, G.B. / Yu, H. / Adler, M. / Whitlow, M. / Ho, E. / Lentz, D. / Polokoff, M.A. / Subramanyam, B. / Wu, J.M. / Zhu, D. / Feldman, R.I. / Arnaiz, D.O.
#1: Journal: To be Published / Year: 2007
Title: Indolinone based Phhosphoinositide-Dependent Kinase-1 (PDK1) inhibitors- Part 2: Optimization of BX-517
Authors: Islam, I. / Brown, G. / Bryant, J. / Hrvatin, P. / Kochanny, M.J. / Phillips, G.B. / Yuan, S. / Adler, M. / Whitlow, M. / Lentz, D. / Polokoff, M.A. / Wu, J. / Shen, J. / Walters, J. / Ho, E. ...Authors: Islam, I. / Brown, G. / Bryant, J. / Hrvatin, P. / Kochanny, M.J. / Phillips, G.B. / Yuan, S. / Adler, M. / Whitlow, M. / Lentz, D. / Polokoff, M.A. / Wu, J. / Shen, J. / Walters, J. / Ho, E. / Subramanyam, B. / Zhu, D. / Feldman, R.I. / Arnaiz, D.O.
#2: Journal: J.Biol.Chem. / Year: 2005
Title: Novel Small Molecule Inhibitors of 3-Phosphoinositide-Dependent Kinase-1.
Authors: Feldman, R.I. / Wu, J.M. / Polokoff, M.A. / Kochanny, M.J. / Dinter, H. / Zhu, D. / Biroc, S.L. / Alicke, B. / Bryant, J. / Yuan, S. / Buckman, B.O. / Lentz, D. / Ferrer, M. / Whitlow, M. / ...Authors: Feldman, R.I. / Wu, J.M. / Polokoff, M.A. / Kochanny, M.J. / Dinter, H. / Zhu, D. / Biroc, S.L. / Alicke, B. / Bryant, J. / Yuan, S. / Buckman, B.O. / Lentz, D. / Ferrer, M. / Whitlow, M. / Adler, M. / Finster, S. / Chang, Z. / Arnaiz, D.O.
#3: Journal: Embo J. / Year: 2002
Title: High Resolution Crystal Structure of the Human Pdk1 Catalytic Domain Defines the Regulatory Phosphopeptide Docking Site.
Authors: Biondi, R.M. / Komander, D. / Thomas, C.C. / Lizcano, J.M. / Deak, M. / Alessi, D.R. / Van Aalten, D.M.F.
History
DepositionApr 1, 2007Deposition site: RCSB / Processing site: RCSB
Revision 1.0Jun 12, 2007Provider: repository / Type: Initial release
Revision 1.1May 1, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Non-polymer description / Version format compliance

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: 3-phosphoinositide-dependent protein kinase 1
hetero molecules


Theoretical massNumber of molelcules
Total (without water)33,9738
Polymers33,1301
Non-polymers8437
Water1,65792
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)125.234, 125.234, 47.696
Angle α, β, γ (deg.)90.00, 90.00, 120.00
Int Tables number154
Space group name H-MP3221

-
Components

#1: Protein 3-phosphoinositide-dependent protein kinase 1 / hPDK1


Mass: 33130.117 Da / Num. of mol.: 1 / Fragment: KINASE DOMAIN
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PDPK1, PDK1 / Plasmid: PDK1-CAT/PBB4.5 / Production host: unidentified baculovirus / Strain (production host): SF-21 CELLS
References: UniProt: O15530, non-specific serine/threonine protein kinase
#2: Chemical ChemComp-SO4 / SULFATE ION / Sulfate


Mass: 96.063 Da / Num. of mol.: 2 / Source method: obtained synthetically / Formula: SO4
#3: Chemical ChemComp-517 / 1-{2-OXO-3-[(1R)-1-(1H-PYRROL-2-YL)ETHYL]-2H-INDOL-5-YL}UREA


Mass: 282.297 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C15H14N4O2
#4: Chemical
ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL / Glycerol


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


Mass: 18.015 Da / Num. of mol.: 92 / 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: 3.2 Å3/Da / Density % sol: 62 %
Crystal growTemperature: 298 K / pH: 7.5
Details: AMMONIUM SULFATE, TRIS, EDTA, VAPOR DIFFUSION, HANGING DROP, temperature 298K, pH 7.50

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.1 / Wavelength: 1
DetectorType: ADSC QUANTUM 4 / Detector: CCD / Date: Oct 2, 2003
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.14→20 Å / Num. obs: 23847 / % possible obs: 99.5 % / Observed criterion σ(I): 4.5 / Redundancy: 3.36 % / Biso Wilson estimate: 8.1 Å2 / Rsym value: 0.115 / Net I/σ(I): 5.89
Reflection shellResolution: 2.14→2.27 Å / Redundancy: 3.3 % / Mean I/σ(I) obs: 1.7 / Rsym value: 0.3769 / % possible all: 99

-
Processing

Software
NameClassification
CNXrefinement
XTALVIEWrefinement
X-GENdata reduction
X-GENdata scaling
CNXphasing
RefinementMethod to determine structure: DIFFERENCE FOURIER PLUS REFINEMENT
Resolution: 2.14→19.91 Å / Rfactor Rfree error: 0.009 / Data cutoff high absF: 67445.14 / Data cutoff low absF: 0 / Isotropic thermal model: RESTRAINED / Cross valid method: THROUGHOUT / σ(F): 2 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflectionSelection details
Rfree0.282 903 3.9 %RANDOM
Rwork0.222 ---
obs0.224 23028 96 %-
all-23831 --
Solvent computationSolvent model: FLAT MODEL / Bsol: 54.01 Å2 / ksol: 0.38 e/Å3
Displacement parametersBiso mean: 17.7 Å2
Baniso -1Baniso -2Baniso -3
1--0.11 Å21.24 Å20 Å2
2---0.11 Å20 Å2
3---0.22 Å2
Refine analyze
FreeObs
Luzzati coordinate error0.35 Å0.27 Å
Luzzati d res low-5 Å
Luzzati sigma a0.33 Å0.31 Å
Refinement stepCycle: LAST / Resolution: 2.14→19.91 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2255 0 55 92 2402
Refine LS restraints
Refine-IDTypeDev idealDev ideal target
X-RAY DIFFRACTIONc_bond_d0.006
X-RAY DIFFRACTIONc_bond_d_na
X-RAY DIFFRACTIONc_bond_d_prot
X-RAY DIFFRACTIONc_angle_d
X-RAY DIFFRACTIONc_angle_d_na
X-RAY DIFFRACTIONc_angle_d_prot
X-RAY DIFFRACTIONc_angle_deg0.9
X-RAY DIFFRACTIONc_angle_deg_na
X-RAY DIFFRACTIONc_angle_deg_prot
X-RAY DIFFRACTIONc_dihedral_angle_d21
X-RAY DIFFRACTIONc_dihedral_angle_d_na
X-RAY DIFFRACTIONc_dihedral_angle_d_prot
X-RAY DIFFRACTIONc_improper_angle_d0.71
X-RAY DIFFRACTIONc_improper_angle_d_na
X-RAY DIFFRACTIONc_improper_angle_d_prot
X-RAY DIFFRACTIONc_mcbond_it1.862
X-RAY DIFFRACTIONc_mcangle_it2.712.5
X-RAY DIFFRACTIONc_scbond_it2.82.5
X-RAY DIFFRACTIONc_scangle_it3.943.5
LS refinement shellResolution: 2.14→2.27 Å / Rfactor Rfree error: 0.025 / Total num. of bins used: 6
RfactorNum. reflection% reflection
Rfree0.3003 147 4.2 %
Rwork0.2767 3392 -
obs--89.2 %
Xplor file
Refine-IDSerial noParam fileTopol file
X-RAY DIFFRACTION1PROTEIN_REP.PPROTEIN.TOP
X-RAY DIFFRACTION2WATER_REP.PARWATER.TOP
X-RAY DIFFRACTION3ION.PARAMION.TOP
X-RAY DIFFRACTION4SPH.PARSPH.TOP
X-RAY DIFFRACTION5517.PAR517.TOP
X-RAY DIFFRACTION6SO4.PARSO4.TOP
X-RAY DIFFRACTION7GOL.PARGOL.TOP

+
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