[English] 日本語
Yorodumi
- PDB-2uzu: PKA structures of indazole-pyridine series of AKT inhibitors -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 2uzu
TitlePKA structures of indazole-pyridine series of AKT inhibitors
Components
  • CAMP-DEPENDENT PROTEIN KINASE INHIBITOR ALPHACAMP-dependent pathway
  • CAMP-DEPENDENT PROTEIN KINASE, ALPHA-CATALYTIC SUBUNITCAMP-dependent pathway
KeywordsTRANSFERASE / CAMP / KINASE / MYRISTATE / LIPOPROTEIN / SERINE/THREONINE-PROTEIN KINASE / PHOSPHORYLATION / PROTEIN KINASE A / NUCLEOTIDE-BINDING / PROTEIN KINASE INHIBITOR / ATP- BINDING / AKT INHIBITORS / NUCLEAR PROTEIN
Function / homology
Function and homology information


CD209 (DC-SIGN) signaling / HDL assembly / Regulation of insulin secretion / Rap1 signalling / Ion homeostasis / PKA activation in glucagon signalling / DARPP-32 events / CREB1 phosphorylation through the activation of Adenylate Cyclase / GPER1 signaling / Factors involved in megakaryocyte development and platelet production ...CD209 (DC-SIGN) signaling / HDL assembly / Regulation of insulin secretion / Rap1 signalling / Ion homeostasis / PKA activation in glucagon signalling / DARPP-32 events / CREB1 phosphorylation through the activation of Adenylate Cyclase / GPER1 signaling / Factors involved in megakaryocyte development and platelet production / Loss of Nlp from mitotic centrosomes / Recruitment of mitotic centrosome proteins and complexes / Loss of proteins required for interphase microtubule organization from the centrosome / Anchoring of the basal body to the plasma membrane / AURKA Activation by TPX2 / RET signaling / Interleukin-3, Interleukin-5 and GM-CSF signaling / Recruitment of NuMA to mitotic centrosomes / VEGFA-VEGFR2 Pathway / PKA activation / GLI3 is processed to GLI3R by the proteasome / MAPK6/MAPK4 signaling / Regulation of PLK1 Activity at G2/M Transition / Hedgehog 'off' state / Mitochondrial protein degradation / cAMP-dependent protein kinase inhibitor activity / cAMP-dependent protein kinase / cAMP-dependent protein kinase activity / cAMP-dependent protein kinase complex / Glucagon-like Peptide-1 (GLP1) regulates insulin secretion / AMP-activated protein kinase activity / Vasopressin regulates renal water homeostasis via Aquaporins / protein kinase A regulatory subunit binding / mesoderm formation / sperm flagellum / negative regulation of TORC1 signaling / protein kinase A signaling / acrosomal vesicle / neuromuscular junction / cellular response to heat / peptidyl-serine phosphorylation / protein kinase activity / protein domain specific binding / protein phosphorylation / protein serine kinase activity / protein serine/threonine kinase activity / perinuclear region of cytoplasm / mitochondrion / ATP binding / nucleus / plasma membrane / cytosol / cytoplasm
Similarity search - Function
cAMP-dependent protein kinase inhibitor / cAMP-dependent protein kinase inhibitor / cAMP-dependent protein kinase catalytic subunit / Extension to Ser/Thr-type protein kinases / AGC-kinase, C-terminal / AGC-kinase C-terminal domain profile. / Transferase(Phosphotransferase) domain 1 / Transferase(Phosphotransferase); domain 1 / Phosphorylase Kinase; domain 1 / Phosphorylase Kinase; domain 1 ...cAMP-dependent protein kinase inhibitor / cAMP-dependent protein kinase inhibitor / cAMP-dependent protein kinase catalytic subunit / Extension to Ser/Thr-type protein kinases / AGC-kinase, C-terminal / AGC-kinase C-terminal domain profile. / 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-L20 / cAMP-dependent protein kinase catalytic subunit alpha / cAMP-dependent protein kinase inhibitor alpha
Similarity search - Component
Biological speciesBOS TAURUS (cattle)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.4 Å
AuthorsZhu, G.D. / Gandhi, V.B. / Gong, J. / Thomas, S. / Woods, K.W. / Song, X. / Li, T. / Diebold, R.B. / Luo, Y. / Liu, X. ...Zhu, G.D. / Gandhi, V.B. / Gong, J. / Thomas, S. / Woods, K.W. / Song, X. / Li, T. / Diebold, R.B. / Luo, Y. / Liu, X. / Guan, R. / Klinghofer, V. / Johnson, E.F. / Bouska, J. / Olson, A. / Marsh, K.C. / Stoll, V.S. / Mamo, M. / Polakowski, J. / Campbell, T.J. / Penning, T.D. / Li, Q. / Rosenberg, S.H. / Giranda, V.L.
CitationJournal: J.Med.Chem. / Year: 2007
Title: Syntheses of Potent, Selective, and Orally Bioavailable Indazole-Pyridine Series of Protein Kinase B/Akt Inhibitors with Reduced Hypotension.
Authors: Zhu, G.D. / Gandhi, V.B. / Gong, J. / Thomas, S. / Woods, K.W. / Song, X. / Li, T. / Diebold, R.B. / Luo, Y. / Liu, X. / Guan, R. / Klinghofer, V. / Johnson, E.F. / Bouska, J. / Olson, A. / ...Authors: Zhu, G.D. / Gandhi, V.B. / Gong, J. / Thomas, S. / Woods, K.W. / Song, X. / Li, T. / Diebold, R.B. / Luo, Y. / Liu, X. / Guan, R. / Klinghofer, V. / Johnson, E.F. / Bouska, J. / Olson, A. / Marsh, K.C. / Stoll, V.S. / Mamo, M. / Polakowski, J. / Campbell, T.J. / Martin, R.L. / Gintant, G.A. / Penning, T.D. / Li, Q. / Rosenberg, S.H. / Giranda, V.L.
History
DepositionMay 1, 2007Deposition site: PDBE / Processing site: PDBE
Revision 1.0Jun 5, 2007Provider: repository / Type: Initial release
Revision 1.1May 8, 2011Group: Version format compliance
Revision 1.2Jul 13, 2011Group: Version format compliance
Revision 1.3May 8, 2024Group: Data collection / Database references / Category: chem_comp_atom / chem_comp_bond / database_2
Item: _database_2.pdbx_DOI / _database_2.pdbx_database_accession

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
E: CAMP-DEPENDENT PROTEIN KINASE, ALPHA-CATALYTIC SUBUNIT
I: CAMP-DEPENDENT PROTEIN KINASE INHIBITOR ALPHA
hetero molecules


Theoretical massNumber of molelcules
Total (without water)41,8403
Polymers41,4422
Non-polymers3971
Water0
1


  • Idetical with deposited unit
  • defined by author&software
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
MethodPQS
Unit cell
Length a, b, c (Å)72.755, 74.748, 80.049
Angle α, β, γ (deg.)90.00, 90.00, 90.00
Int Tables number19
Space group name H-MP212121

-
Components

#1: Protein CAMP-DEPENDENT PROTEIN KINASE, ALPHA-CATALYTIC SUBUNIT / CAMP-dependent pathway / PKA C-ALPHA / PROTEIN KINASE A


Mass: 39216.059 Da / Num. of mol.: 1 / Fragment: RESIDUES 15-350
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) BOS TAURUS (cattle) / Production host: ESCHERICHIA COLI (E. coli) / References: UniProt: P00517, cAMP-dependent protein kinase
#2: Protein/peptide CAMP-DEPENDENT PROTEIN KINASE INHIBITOR ALPHA / CAMP-dependent pathway / PKI-ALPHA


Mass: 2226.411 Da / Num. of mol.: 1 / Fragment: RESIDUES 5-24
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) BOS TAURUS (cattle) / Production host: ESCHERICHIA COLI (E. coli) / References: UniProt: Q3SX13
#3: Chemical ChemComp-L20 / (2S)-1-(1H-INDOL-3-YL)-3-{[5-(3-METHYL-1H-INDAZOL-5-YL)PYRIDIN-3-YL]OXY}PROPAN-2-AMINE


Mass: 397.472 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C24H23N5O

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.63 Å3/Da / Density % sol: 53.16 %

-
Data collection

DiffractionMean temperature: 100 K
Diffraction sourceSource: SYNCHROTRON / Site: APS / Beamline: 17-ID / Wavelength: 1
DetectorType: ADSC CCD / Detector: CCD
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 1 Å / Relative weight: 1
ReflectionResolution: 2.4→50 Å / Num. obs: 17714 / % possible obs: 98.9 % / Observed criterion σ(I): 2 / Redundancy: 4.9 % / Biso Wilson estimate: 28.9 Å2 / Rmerge(I) obs: 0.07 / Net I/σ(I): 8
Reflection shellResolution: 2.4→2.49 Å / Redundancy: 3.3 % / Rmerge(I) obs: 0.41 / Mean I/σ(I) obs: 5 / % possible all: 91

-
Processing

Software
NameVersionClassification
CNS1refinement
HKL-2000data reduction
SCALEPACKdata scaling
CNXphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.4→20 Å / Rfactor Rfree error: 0.008 / Data cutoff high absF: 10000 / Isotropic thermal model: OVERALL / Cross valid method: THROUGHOUT / σ(F): 0
RfactorNum. reflection% reflectionSelection details
Rfree0.3707 1605 9.1 %RANDOM
Rwork0.3183 ---
obs0.3183 16204 92 %-
Solvent computationSolvent model: FLAT MODEL / Bsol: 47.1505 Å2 / ksol: 0.423073 e/Å3
Displacement parametersBiso mean: 36 Å2
Baniso -1Baniso -2Baniso -3
1--5.293 Å20 Å20 Å2
2--0.695 Å20 Å2
3---4.598 Å2
Refine analyze
FreeObs
Luzzati coordinate error0.48 Å0.37 Å
Luzzati d res low-5 Å
Luzzati sigma a0.43 Å0.31 Å
Refinement stepCycle: LAST / Resolution: 2.4→20 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2927 0 30 0 2957
Refine LS restraints
Refine-IDTypeDev ideal
X-RAY DIFFRACTIONc_bond_d0.008
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_deg1.3
X-RAY DIFFRACTIONc_angle_deg_na
X-RAY DIFFRACTIONc_angle_deg_prot
X-RAY DIFFRACTIONc_dihedral_angle_d22.1
X-RAY DIFFRACTIONc_dihedral_angle_d_na
X-RAY DIFFRACTIONc_dihedral_angle_d_prot
X-RAY DIFFRACTIONc_improper_angle_d0.75
X-RAY DIFFRACTIONc_improper_angle_d_na
X-RAY DIFFRACTIONc_improper_angle_d_prot
X-RAY DIFFRACTIONc_mcbond_it
X-RAY DIFFRACTIONc_mcangle_it
X-RAY DIFFRACTIONc_scbond_it
X-RAY DIFFRACTIONc_scangle_it
LS refinement shellResolution: 2.4→2.55 Å / Rfactor Rfree error: 0.026 / Total num. of bins used: 6
RfactorNum. reflection% reflection
Rfree0.385 226 9.8 %
Rwork0.329 2079 -
obs--79.8 %
Xplor file
Refine-IDSerial noParam fileTopol file
X-RAY DIFFRACTION1PROTEIN_REP.PARAMPROTEIN.TOP
X-RAY DIFFRACTION2WATER_REP.PARAM
X-RAY DIFFRACTION3ION.PARAM
X-RAY DIFFRACTION4LIG.PAR

+
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