[English] 日本語
Yorodumi
- PDB-1z5m: Crystal Structure Of N1-[3-[[5-bromo-2-[[3-[(1-pyrrolidinylcarbon... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 1z5m
TitleCrystal Structure Of N1-[3-[[5-bromo-2-[[3-[(1-pyrrolidinylcarbonyl)amino]phenyl]amino]-4-pyrimidinyl]amino]propyl]-2,2-dimethylpropanediamide Complexed with Human PDK1
Components3-phosphoinositide dependent protein kinase-1
KeywordsTRANSFERASE / PROTEIN INHIBITOR COMPLEX / SERINE KINASE
Function / homology
Function and homology information


intracellular signaling cassette / 3-phosphoinositide-dependent protein kinase activity / Activation of AKT2 / regulation of mast cell degranulation / type B pancreatic cell development / negative regulation of toll-like receptor signaling pathway / RSK activation / regulation of canonical NF-kappaB signal transduction / hyperosmotic response / positive regulation of vascular endothelial cell proliferation ...intracellular signaling cassette / 3-phosphoinositide-dependent protein kinase activity / Activation of AKT2 / regulation of mast cell degranulation / type B pancreatic cell development / negative regulation of toll-like receptor signaling pathway / RSK activation / regulation of canonical NF-kappaB signal transduction / hyperosmotic response / positive regulation of vascular endothelial cell proliferation / negative regulation of cardiac muscle cell apoptotic process / phospholipase activator activity / positive regulation of sprouting angiogenesis / Constitutive Signaling by AKT1 E17K in Cancer / CD28 dependent PI3K/Akt signaling / positive regulation of blood vessel endothelial cell migration / Role of LAT2/NTAL/LAB on calcium mobilization / negative regulation of endothelial cell apoptotic process / Estrogen-stimulated signaling through PRKCZ / vascular endothelial cell response to laminar fluid shear stress / SARS-CoV-2 targets host intracellular signalling and regulatory pathways / phospholipase binding / SARS-CoV-1 targets host intracellular signalling and regulatory pathways / GPVI-mediated activation cascade / RHO GTPases activate PKNs / T cell costimulation / extrinsic apoptotic signaling pathway / Integrin signaling / insulin-like growth factor receptor signaling pathway / cellular response to epidermal growth factor stimulus / positive regulation of release of sequestered calcium ion into cytosol / VEGFR2 mediated cell proliferation / VEGFR2 mediated vascular permeability / cell projection / positive regulation of protein localization to plasma membrane / phosphatidylinositol 3-kinase/protein kinase B signal transduction / negative regulation of transforming growth factor beta receptor signaling pathway / calcium-mediated signaling / CLEC7A (Dectin-1) signaling / FCERI mediated NF-kB activation / epidermal growth factor receptor signaling pathway / cellular response to insulin stimulus / positive regulation of angiogenesis / Regulation of TP53 Degradation / Downstream TCR signaling / G beta:gamma signalling through PI3Kgamma / insulin receptor signaling pathway / cell migration / PIP3 activates AKT signaling / protein autophosphorylation / actin cytoskeleton organization / cytoplasmic vesicle / High laminar flow shear stress activates signaling by PIEZO1 and PECAM1:CDH5:KDR in endothelial cells / protein phosphorylation / positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction / non-specific serine/threonine protein kinase / postsynaptic density / intracellular signal transduction / protein serine kinase activity / focal adhesion / protein serine/threonine kinase activity / ATP binding / nucleus / plasma membrane / cytosol / cytoplasm
Similarity search - Function
PDK1-type, PH domain / PH domain / PDPK1 family / : / PH-like domain superfamily / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Serine/threonine-protein kinase, active site ...PDK1-type, PH domain / PH domain / PDPK1 family / : / PH-like domain superfamily / 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-LI8 / 3-phosphoinositide-dependent protein kinase 1
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.17 Å
AuthorsWhitlow, M. / Adler, M.
Citation
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.
#1: 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
DepositionMar 18, 2005Deposition site: RCSB / Processing site: RCSB
Revision 1.0Apr 19, 2005Provider: repository / Type: Initial release
Revision 1.1Apr 30, 2008Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Non-polymer description / Version format compliance
Revision 1.3Oct 11, 2017Group: Refinement description / Category: software / Item: _software.name
Revision 1.4Aug 23, 2023Group: Data collection / Database references ...Data collection / Database references / Derived calculations / Refinement description
Category: chem_comp_atom / chem_comp_bond ...chem_comp_atom / chem_comp_bond / database_2 / pdbx_initial_refinement_model / struct_conn / struct_ref_seq_dif / struct_site
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession ..._database_2.pdbx_DOI / _database_2.pdbx_database_accession / _struct_conn.pdbx_leaving_atom_flag / _struct_ref_seq_dif.details / _struct_site.pdbx_auth_asym_id / _struct_site.pdbx_auth_comp_id / _struct_site.pdbx_auth_seq_id
Revision 1.5Oct 30, 2024Group: Structure summary / Category: pdbx_entry_details / pdbx_modification_feature
Remark 600HETEROGEN THE INHIBITION CONSTANT (KI APPARENT) FOR N-(3-{[5-BROMO-2-({3-[(PYRROLIDIN-1- YLCARBONYL) ...HETEROGEN THE INHIBITION CONSTANT (KI APPARENT) FOR N-(3-{[5-BROMO-2-({3-[(PYRROLIDIN-1- YLCARBONYL)AMINO]PHENYL}AMINO)PYRIMIDIN -4-YL]AMINO}PROPYL)-2,2-DIMETHYLMALONAMIDE AGAINST PDK1 WAS MEASURED AS 30 NM (N=5) DIRECT MEASURE PDK1 ACTIVITY WAS PERFORMED BY THE FOLLOWING PROTOCOL: THE FINAL ASSAY MIXTURE (60 UL) CONTAINED 50 MM TRIS- HCL, PH 7.5, 0.1 MM EGTA, 0.1 MM EDTA, 0.1% BETA-MERCAPTOETHANOL, 1 MG/ML BOVINE SERUM ALBUMIN, 10 MM MGOAC, 10 UM ATP, 0.2 UCI OF [GAMMA-33P]ATP, 7.5 UM OF SUBSTRATE PEPTIDE (H2NARRRGVTTKTFCGT) AND 60 NG OF PURIFIED RECOMBINANT HUMAN PDK1. AFTER 4 H AT ROOM TEMPERATURE, WE ADDED 25 MM EDTA AND SPOTTED A PORTION OF THE REACTION MIXTURE ON WHATMAN P81 PHOSPHOCELLULOSE PAPER. THE FILTER PAPER WAS WASHED 3 TIMES WITH 0.75% PHOSPHORIC ACID AND ONCE WITH ACETONE. AFTER DRYING, THE FILTER-BOUND LABELED PEPTIDE WAS QUANTIFIED USING A FUJI PHOSPHOIMAGER.

-
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)34,0857
Polymers33,1301
Non-polymers9556
Water1,33374
1


  • Idetical with deposited unit
  • defined by author
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Unit cell
Length a, b, c (Å)124.61, 124.61, 46.97
Angle α, β, γ (deg.)90.0, 90.0, 120.0
Int Tables number154
Space group name H-MP3221

-
Components

-
Protein , 1 types, 1 molecules A

#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, EC: 2.7.1.37

-
Non-polymers , 5 types, 80 molecules

#2: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#3: Chemical ChemComp-CL / CHLORIDE ION


Mass: 35.453 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: Cl
#4: Chemical ChemComp-LI8 / N-(3-{[5-BROMO-2-({3-[(PYRROLIDIN-1-YLCARBONYL)AMINO]PHENYL}AMINO)PYRIMIDIN-4-YL]AMINO}PROPYL)-2,2-DIMETHYLMALONAMIDE


Mass: 547.448 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C23H31BrN8O3
#5: Chemical ChemComp-GOL / GLYCEROL / GLYCERIN / PROPANE-1,2,3-TRIOL


Mass: 92.094 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: C3H8O3
#6: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 74 / Source method: isolated from a natural source / Formula: H2O

-
Details

Has protein modificationY

-
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 / Method: vapor diffusion, hanging drop / pH: 7.5
Details: Ammonium Sulfate, Tris, EDTA, pH 7.5, VAPOR DIFFUSION, HANGING DROP, temperature 298K

-
Data collection

DiffractionMean temperature: 94.2 K
Diffraction sourceSource: SYNCHROTRON / Site: ALS / Beamline: 5.0.1 / Wavelength: 1 Å
DetectorType: ADSC QUANTUM 4 / Detector: CCD / Date: Jun 22, 2003
RadiationMonochromator: single crystal Si(220); cylindrically bent / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.17→20 Å / Num. all: 22440 / Num. obs: 21597 / % possible obs: 96.2 % / Observed criterion σ(F): 0 / Observed criterion σ(I): -3 / Redundancy: 3.417 % / Biso Wilson estimate: 36.4 Å2 / Rsym value: 0.0874 / Net I/σ(I): 8.33
Reflection shellResolution: 2.17→2.31 Å / Redundancy: 2.77 % / Mean I/σ(I) obs: 2.14 / Num. unique all: 3380 / Rsym value: 0.347 / % possible all: 91.2

-
Processing

Software
NameVersionClassification
Blu-Icedata collection
X-GENdata reduction
MOLREPphasing
X-PLOR3.1refinement
X-GENdata scaling
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: PDK1 Homology model built from pdb entry 1O6L

1o6l


Resolution: 2.17→8 Å / Isotropic thermal model: Overall / σ(F): 2 / Stereochemistry target values: Engh & Huber
RfactorNum. reflection% reflectionSelection details
Rfree0.269 915 -RANDOM
Rwork0.212 ---
all0.232 22377 --
obs0.219 21580 96.4 %-
Displacement parametersBiso mean: 25.7 Å2
Baniso -1Baniso -2Baniso -3
1-1.18 Å21.61 Å20 Å2
2--1.18 Å20 Å2
3----2.35 Å2
Refinement stepCycle: LAST / Resolution: 2.17→8 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2255 0 59 74 2388
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONx_bond_d0.012
X-RAY DIFFRACTIONx_angle_deg1.77
X-RAY DIFFRACTIONx_improper_angle_d1.46
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkRefine-IDNum. reflection obs% reflection obs (%)
2.17-2.270.373850.309X-RAY DIFFRACTION209490
2.27-2.380.331100.29X-RAY DIFFRACTION238095.9
2.38-2.530.3181030.268X-RAY DIFFRACTION252998.2
2.53-2.720.341240.251X-RAY DIFFRACTION261098.6
2.72-2.980.2551200.222X-RAY DIFFRACTION262897.9
2.98-3.380.2651070.201X-RAY DIFFRACTION263697.6
3.38-4.150.221180.163X-RAY DIFFRACTION267797.6
4.15-80.235900.179X-RAY DIFFRACTION267595.7

+
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