[English] 日本語
Yorodumi
- PDB-7nh5: Co-Crystal Structure of Akt1 in Complex with Covalent-Allosteric ... -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7nh5
TitleCo-Crystal Structure of Akt1 in Complex with Covalent-Allosteric Akt Inhibitor 6
ComponentsRAC-alpha serine/threonine-protein kinase
KeywordsTRANSFERASE / Akt1 / Akt2 / Akt3 / covalent-allosteric
Function / homology
Function and homology information


glycogen cell differentiation involved in embryonic placenta development / regulation of tRNA methylation / negative regulation of protein maturation / response to insulin-like growth factor stimulus / potassium channel activator activity / negative regulation of protein localization to lysosome / positive regulation of protein localization to endoplasmic reticulum / negative regulation of lymphocyte migration / maintenance of protein location in mitochondrion / cellular response to decreased oxygen levels ...glycogen cell differentiation involved in embryonic placenta development / regulation of tRNA methylation / negative regulation of protein maturation / response to insulin-like growth factor stimulus / potassium channel activator activity / negative regulation of protein localization to lysosome / positive regulation of protein localization to endoplasmic reticulum / negative regulation of lymphocyte migration / maintenance of protein location in mitochondrion / cellular response to decreased oxygen levels / cellular response to rapamycin / regulation of type B pancreatic cell development / AKT-mediated inactivation of FOXO1A / maternal placenta development / Negative regulation of the PI3K/AKT network / negative regulation of long-chain fatty acid import across plasma membrane / establishment of protein localization to mitochondrion / negative regulation of fatty acid beta-oxidation / regulation of glycogen biosynthetic process / AKT phosphorylates targets in the nucleus / cellular response to oxidised low-density lipoprotein particle stimulus / positive regulation of I-kappaB phosphorylation / negative regulation of cilium assembly / Butyrate Response Factor 1 (BRF1) binds and destabilizes mRNA / RUNX2 regulates genes involved in cell migration / positive regulation of organ growth / response to fluid shear stress / cellular response to peptide / negative regulation of endopeptidase activity / interleukin-18-mediated signaling pathway / fibroblast migration / MTOR signalling / positive regulation of sodium ion transport / mammary gland epithelial cell differentiation / negative regulation of protein serine/threonine kinase activity / positive regulation of glucose metabolic process / RAB GEFs exchange GTP for GDP on RABs / response to growth factor / cellular response to granulocyte macrophage colony-stimulating factor stimulus / negative regulation of leukocyte cell-cell adhesion / positive regulation of protein localization to cell surface / phosphatidylinositol-3,4-bisphosphate binding / positive regulation of endodeoxyribonuclease activity / peripheral nervous system myelin maintenance / glycogen biosynthetic process / sphingosine-1-phosphate receptor signaling pathway / protein serine/threonine kinase inhibitor activity / cell migration involved in sprouting angiogenesis / positive regulation of fibroblast migration / response to growth hormone / anoikis / AKT phosphorylates targets in the cytosol / response to food / non-canonical NF-kappaB signal transduction / labyrinthine layer blood vessel development / response to UV-A / regulation of myelination / regulation of postsynapse organization / Regulation of TP53 Activity through Association with Co-factors / KSRP (KHSRP) binds and destabilizes mRNA / execution phase of apoptosis / negative regulation of macroautophagy / CTLA4 inhibitory signaling / negative regulation of cGAS/STING signaling pathway / mammalian oogenesis stage / negative regulation of Notch signaling pathway / activation-induced cell death of T cells / regulation of neuron projection development / negative regulation of release of cytochrome c from mitochondria / Constitutive Signaling by AKT1 E17K in Cancer / phosphatidylinositol-3,4,5-trisphosphate binding / behavioral response to pain / CD28 dependent PI3K/Akt signaling / apoptotic mitochondrial changes / Regulation of localization of FOXO transcription factors / positive regulation of cyclin-dependent protein serine/threonine kinase activity / negative regulation of extrinsic apoptotic signaling pathway in absence of ligand / positive regulation of glycogen biosynthetic process / Activation of BAD and translocation to mitochondria / Estrogen-dependent nuclear events downstream of ESR-membrane signaling / positive regulation of blood vessel endothelial cell migration / cellular response to vascular endothelial growth factor stimulus / TOR signaling / positive regulation of fat cell differentiation / positive regulation of G1/S transition of mitotic cell cycle / SARS-CoV-2 targets host intracellular signalling and regulatory pathways / eNOS activation / canonical NF-kappaB signal transduction / Cyclin E associated events during G1/S transition / phosphorylation / positive regulation of lipid biosynthetic process / negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway / Cyclin A:Cdk2-associated events at S phase entry / Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulation / lipopolysaccharide-mediated signaling pathway / 14-3-3 protein binding / Regulation of TP53 Activity through Acetylation / negative regulation of protein ubiquitination / striated muscle cell differentiation / positive regulation of endothelial cell proliferation
Similarity search - Function
Protein kinase B alpha, catalytic domain / Protein Kinase B, pleckstrin homology domain / Protein kinase, C-terminal / Protein kinase C terminal domain / Extension to Ser/Thr-type protein kinases / AGC-kinase, C-terminal / AGC-kinase C-terminal domain profile. / PH domain / PH domain profile. / Pleckstrin homology domain. ...Protein kinase B alpha, catalytic domain / Protein Kinase B, pleckstrin homology domain / Protein kinase, C-terminal / Protein kinase C terminal domain / Extension to Ser/Thr-type protein kinases / AGC-kinase, C-terminal / AGC-kinase C-terminal domain profile. / PH domain / PH domain profile. / Pleckstrin homology domain. / Pleckstrin homology domain / PH-like domain superfamily / 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
Similarity search - Domain/homology
ACETATE ION / Chem-UC8 / RAC-alpha serine/threonine-protein kinase
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 1.9 Å
AuthorsLandel, I. / Mueller, M.P. / Rauh, D.
Funding support Germany, 4items
OrganizationGrant numberCountry
German Federal Ministry for Education and ResearchBMBF 01GS08104 Germany
German Federal Ministry for Education and Research01ZX1303C Germany
European Regional Development FundEFRE-800400 Germany
German Research Foundation (DFG) Germany
CitationJournal: Nat Commun / Year: 2021
Title: Cellular model system to dissect the isoform-selectivity of Akt inhibitors.
Authors: Quambusch, L. / Depta, L. / Landel, I. / Lubeck, M. / Kirschner, T. / Nabert, J. / Uhlenbrock, N. / Weisner, J. / Kostka, M. / Levy, L.M. / Schultz-Fademrecht, C. / Glanemann, F. / Althoff, ...Authors: Quambusch, L. / Depta, L. / Landel, I. / Lubeck, M. / Kirschner, T. / Nabert, J. / Uhlenbrock, N. / Weisner, J. / Kostka, M. / Levy, L.M. / Schultz-Fademrecht, C. / Glanemann, F. / Althoff, K. / Muller, M.P. / Siveke, J.T. / Rauh, D.
History
DepositionFeb 10, 2021Deposition site: PDBE / Processing site: PDBE
Revision 1.0Sep 8, 2021Provider: repository / Type: Initial release
Revision 1.1Sep 29, 2021Group: Data collection / Database references
Category: citation / citation_author ...citation / citation_author / pdbx_database_proc / pdbx_struct_ref_seq_depositor_info
Item: _citation.journal_volume / _citation.page_first ..._citation.journal_volume / _citation.page_first / _citation.page_last / _citation.pdbx_database_id_PubMed / _citation.title / _citation_author.name / _pdbx_struct_ref_seq_depositor_info.db_seq_one_letter_code
Revision 1.2Jan 31, 2024Group: Data collection / Refinement description
Category: chem_comp_atom / chem_comp_bond / pdbx_initial_refinement_model

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: RAC-alpha serine/threonine-protein kinase
hetero molecules


Theoretical massNumber of molelcules
Total (without water)52,3943
Polymers51,7461
Non-polymers6482
Water1,49583
1


  • Idetical with deposited unit
  • defined by author&software
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area230 Å2
ΔGint-0 kcal/mol
Surface area17880 Å2
MethodPISA
Unit cell
Length a, b, c (Å)70.650, 71.410, 91.020
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number19
Space group name H-MP212121
Space group name HallP2ac2ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x,y+1/2,-z+1/2
#4: -x+1/2,-y,z+1/2

-
Components

#1: Protein RAC-alpha serine/threonine-protein kinase / Protein kinase B / PKB / Protein kinase B alpha / PKB alpha / Proto-oncogene c-Akt / RAC-PK-alpha


Mass: 51746.035 Da / Num. of mol.: 1 / Mutation: E114A, E115A, E116A
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: AKT1, PKB, RAC / Production host: Spodoptera frugiperda (fall armyworm)
References: UniProt: P31749, non-specific serine/threonine protein kinase
#2: Chemical ChemComp-ACT / ACETATE ION


Mass: 59.044 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C2H3O2
#3: Chemical ChemComp-UC8 / ~{N}-methyl-6-[4-[[4-[2-oxidanylidene-6-(propanoylamino)-3~{H}-benzimidazol-1-yl]piperidin-1-yl]methyl]phenyl]-5-phenyl-pyridine-3-carboxamide


Mass: 588.699 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C35H36N6O3 / Feature type: SUBJECT OF INVESTIGATION
#4: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 83 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.22 Å3/Da / Density % sol: 44.56 %
Crystal growTemperature: 293 K / Method: vapor diffusion, hanging drop / pH: 6.5
Details: 1.25 mM Na-acetate, 3.75 mM Na-citrate, 18% v/v PEG 2000 MME, pH 6.5, 3 mg/mL Akt1 (in 25 mM TRIS, 100 mM NaCl, 10% v/v Glycerol, 5 mM DTT, pH 7.5), 1 uL reservoir + 1 uL protein solution

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: SLS / Beamline: X10SA / Wavelength: 0.99998 Å
DetectorType: DECTRIS EIGER2 X 16M / Detector: PIXEL / Date: Jun 22, 2020
RadiationMonochromator: Si(111) / Protocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.99998 Å / Relative weight: 1
ReflectionResolution: 1.9→43.97 Å / Num. obs: 36972 / % possible obs: 100 % / Redundancy: 13.5 % / Biso Wilson estimate: 47.14 Å2 / CC1/2: 1 / Rmerge(I) obs: 0.048 / Rrim(I) all: 0.05 / Net I/σ(I): 25.85
Reflection shellResolution: 1.9→2 Å / Redundancy: 14.1 % / Rmerge(I) obs: 1.817 / Mean I/σ(I) obs: 1.47 / Num. unique obs: 5186 / CC1/2: 0.679 / Rrim(I) all: 1.885 / % possible all: 100

-
Processing

Software
NameVersionClassification
PHENIX1.17.1_3660refinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT
Starting model: 6HHG

6hhg


Resolution: 1.9→43.97 Å / SU ML: 0.2459 / Cross valid method: FREE R-VALUE / σ(F): 1.35 / Phase error: 24.9603
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.2284 1849 5 %
Rwork0.1998 35115 -
obs0.2012 36964 99.96 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.11 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 57.66 Å2
Refinement stepCycle: LAST / Resolution: 1.9→43.97 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms3101 0 48 83 3232
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.01043309
X-RAY DIFFRACTIONf_angle_d1.08354485
X-RAY DIFFRACTIONf_chiral_restr0.0601470
X-RAY DIFFRACTIONf_plane_restr0.0068571
X-RAY DIFFRACTIONf_dihedral_angle_d25.73781224
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
1.9-1.950.37231400.3482654X-RAY DIFFRACTION99.93
1.95-2.010.31831390.27172653X-RAY DIFFRACTION100
2.01-2.070.27951400.23472660X-RAY DIFFRACTION99.96
2.07-2.150.2771410.2362679X-RAY DIFFRACTION99.96
2.15-2.230.26291420.22592680X-RAY DIFFRACTION100
2.23-2.340.28261400.21512667X-RAY DIFFRACTION100
2.34-2.460.24541410.21882681X-RAY DIFFRACTION99.96
2.46-2.610.27881410.22622681X-RAY DIFFRACTION100
2.61-2.810.30441420.23752696X-RAY DIFFRACTION100
2.81-3.10.25251430.22772709X-RAY DIFFRACTION100
3.1-3.550.24111430.21242719X-RAY DIFFRACTION100
3.55-4.470.19221450.16872763X-RAY DIFFRACTION99.97
4.47-43.970.1851520.17462873X-RAY DIFFRACTION99.8
Refinement TLS params.Method: refined / Origin x: 13.9783080786 Å / Origin y: -11.876787987 Å / Origin z: -15.6412139471 Å
111213212223313233
T0.264305901388 Å2-0.0198194871315 Å2-0.0462863331439 Å2-0.309011713915 Å20.021764176537 Å2--0.284130203076 Å2
L1.78065259052 °20.584361876126 °2-0.0775150443221 °2-1.98663642173 °2-0.000747567389177 °2--1.61470805729 °2
S0.00129235707512 Å °0.0197978234148 Å °-0.0583561508498 Å °-0.0245010965514 Å °-0.0944099535668 Å °-0.0543304654634 Å °-0.0671033347829 Å °0.0101045373212 Å °0.0894143800223 Å °
Refinement TLS groupSelection details: (chain A)

+
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