[English] 日本語
Yorodumi
- PDB-9ic2: Structure of AMPK-alpha2-kinase domain bound to BAY-3827 -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 9ic2
TitleStructure of AMPK-alpha2-kinase domain bound to BAY-3827
Components5'-AMP-activated protein kinase catalytic subunit alpha-2
KeywordsSIGNALING PROTEIN / Kinase
Function / homology
Function and homology information


[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase / [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity / regulation of stress granule assembly / AMPK inhibits chREBP transcriptional activation activity / histone H2BS36 kinase activity / AMP-activated protein kinase activity / lipid droplet disassembly / Lipophagy / nucleotide-activated protein kinase complex / negative regulation of hepatocyte apoptotic process ...[hydroxymethylglutaryl-CoA reductase (NADPH)] kinase / [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase activity / regulation of stress granule assembly / AMPK inhibits chREBP transcriptional activation activity / histone H2BS36 kinase activity / AMP-activated protein kinase activity / lipid droplet disassembly / Lipophagy / nucleotide-activated protein kinase complex / negative regulation of hepatocyte apoptotic process / Carnitine shuttle / Energy dependent regulation of mTOR by LKB1-AMPK / negative regulation of TOR signaling / Activation of PPARGC1A (PGC-1alpha) by phosphorylation / Nuclear events mediated by NFE2L2 / protein localization to lipid droplet / negative regulation of tubulin deacetylation / cholesterol biosynthetic process / Macroautophagy / lipid biosynthetic process / response to muscle activity / positive regulation of macroautophagy / regulation of macroautophagy / fatty acid homeostasis / cellular response to nutrient levels / cellular response to glucose starvation / energy homeostasis / Activation of AMPK downstream of NMDARs / positive regulation of protein localization / negative regulation of TORC1 signaling / positive regulation of autophagy / protein serine/threonine/tyrosine kinase activity / cellular response to calcium ion / regulation of microtubule cytoskeleton organization / positive regulation of glycolytic process / TP53 Regulates Metabolic Genes / Translocation of SLC2A4 (GLUT4) to the plasma membrane / cellular response to glucose stimulus / regulation of circadian rhythm / autophagy / Wnt signaling pathway / cellular response to xenobiotic stimulus / cytoplasmic stress granule / fatty acid biosynthetic process / rhythmic process / cellular response to prostaglandin E stimulus / glucose homeostasis / cellular response to oxidative stress / Regulation of TP53 Activity through Phosphorylation / protein phosphorylation / non-specific serine/threonine protein kinase / protein kinase activity / nuclear speck / ciliary basal body / axon / negative regulation of gene expression / protein serine kinase activity / neuronal cell body / protein serine/threonine kinase activity / dendrite / chromatin binding / negative regulation of apoptotic process / Golgi apparatus / signal transduction / nucleoplasm / ATP binding / metal ion binding / nucleus / cytosol / cytoplasm
Similarity search - Function
PRKAA2, UBA-like autoinhibitory domain / 5'-AMP-activated protein kinase catalytic subunit alpha-2, C-terminal / : / AMP-activated protein kinase, alpha subunit, autoinhibitory domain / AMPK, C-terminal adenylate sensor domain / Adenylate sensor of SNF1-like protein kinase / KA1 domain/Ssp2, C-terminal / Serine/threonine-protein kinase, active site / Serine/Threonine protein kinases active-site signature. / Protein kinase domain ...PRKAA2, UBA-like autoinhibitory domain / 5'-AMP-activated protein kinase catalytic subunit alpha-2, C-terminal / : / AMP-activated protein kinase, alpha subunit, autoinhibitory domain / AMPK, C-terminal adenylate sensor domain / Adenylate sensor of SNF1-like protein kinase / KA1 domain/Ssp2, C-terminal / 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
: / 5'-AMP-activated protein kinase catalytic subunit alpha-2
Similarity search - Component
Biological speciesHomo sapiens (human)
MethodX-RAY DIFFRACTION / SYNCHROTRON / MOLECULAR REPLACEMENT / Resolution: 2.5 Å
AuthorsAhangar, M.S. / Zeqiraj, E. / Fraguas Bringas, C. / Sakamoto, K.
Funding support United Kingdom, 1items
OrganizationGrant numberCountry
Wellcome Trust United Kingdom
CitationJournal: To Be Published
Title: Structure of AMPK-alpha2-kinase domain bound to BAY-3827
Authors: Ahangar, M.S. / Zeqiraj, E.
History
DepositionFeb 14, 2025Deposition site: PDBE / Processing site: PDBE
Revision 1.0Sep 3, 2025Provider: repository / Type: Initial release

-
Structure visualization

Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: 5'-AMP-activated protein kinase catalytic subunit alpha-2
hetero molecules


Theoretical massNumber of molelcules
Total (without water)32,2236
Polymers31,5861
Non-polymers6385
Water1,11762
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_555x,y,z1
Buried area320 Å2
ΔGint-24 kcal/mol
Surface area12940 Å2
Unit cell
Length a, b, c (Å)59.176, 117.778, 38.327
Angle α, β, γ (deg.)90.000, 90.000, 90.000
Int Tables number18
Space group name H-MP21212
Space group name HallP22ab
Symmetry operation#1: x,y,z
#2: x+1/2,-y+1/2,-z
#3: -x+1/2,y+1/2,-z
#4: -x,-y,z
Components on special symmetry positions
IDModelComponents
11A-436-

HOH

21A-451-

HOH

31A-452-

HOH

-
Components

#1: Protein 5'-AMP-activated protein kinase catalytic subunit alpha-2 / AMPK subunit alpha-2 / Acetyl-CoA carboxylase kinase / ACACA kinase / Hydroxymethylglutaryl-CoA ...AMPK subunit alpha-2 / Acetyl-CoA carboxylase kinase / ACACA kinase / Hydroxymethylglutaryl-CoA reductase kinase / HMGCR kinase


Mass: 31585.754 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: The protein sequence contain first amino acid Gly from the Tev site followed by AMPK-alpha2 (6-280 amino acids). The second amino acid Lys in the protein chain is assigned residue number 6 ...Details: The protein sequence contain first amino acid Gly from the Tev site followed by AMPK-alpha2 (6-280 amino acids). The second amino acid Lys in the protein chain is assigned residue number 6 matching with the actual protein sequence.
Source: (gene. exp.) Homo sapiens (human) / Gene: PRKAA2, AMPK, AMPK2 / Production host: Escherichia coli BL21(DE3) (bacteria)
References: UniProt: P54646, non-specific serine/threonine protein kinase, [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase
#2: Chemical ChemComp-A1I1Y / ~{N}-[5-(3,5-dicyano-1,2,6-trimethyl-4~{H}-pyridin-4-yl)-6-fluoranyl-7-methyl-1~{H}-indazol-3-yl]-2-ethyl-benzamide


Mass: 468.525 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C27H25FN6O / Feature type: SUBJECT OF INVESTIGATION
#3: Chemical ChemComp-MG / MAGNESIUM ION


Mass: 24.305 Da / Num. of mol.: 3 / Source method: obtained synthetically / Formula: Mg
#4: Chemical ChemComp-SO4 / SULFATE ION


Mass: 96.063 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: SO4
#5: Water ChemComp-HOH / water


Mass: 18.015 Da / Num. of mol.: 62 / Source method: isolated from a natural source / Formula: H2O
Has ligand of interestY
Has protein modificationY

-
Experimental details

-
Experiment

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

-
Sample preparation

CrystalDensity Matthews: 2.11 Å3/Da / Density % sol: 41.82 %
Crystal growTemperature: 295 K / Method: vapor diffusion
Details: 0.1M Ammonium sulfate, 0.3 Sodium formate, 0.1M Sodium cacodylate pH 6.5, 3% Gamma-PGA, 3% PEG 20000

-
Data collection

DiffractionMean temperature: 100 K / Serial crystal experiment: N
Diffraction sourceSource: SYNCHROTRON / Site: Diamond / Beamline: I24 / Wavelength: 0.6199 Å
DetectorType: DECTRIS PILATUS 6M / Detector: PIXEL / Date: Dec 10, 2023
RadiationProtocol: SINGLE WAVELENGTH / Monochromatic (M) / Laue (L): M / Scattering type: x-ray
Radiation wavelengthWavelength: 0.6199 Å / Relative weight: 1
ReflectionResolution: 2.5→58.89 Å / Num. obs: 10021 / % possible obs: 99.9 % / Redundancy: 6.5 % / Biso Wilson estimate: 39.04 Å2 / CC1/2: 0.997 / CC star: 0.999 / Rmerge(I) obs: 0.074 / Rrim(I) all: 0.081 / Net I/σ(I): 15.7
Reflection shellResolution: 2.5→2.56 Å / Num. unique obs: 890 / CC1/2: 0.944

-
Processing

Software
NameVersionClassification
PHENIX1.21.1_5286refinement
autoPROCdata reduction
Aimlessdata scaling
PHASERphasing
RefinementMethod to determine structure: MOLECULAR REPLACEMENT / Resolution: 2.5→58.89 Å / SU ML: 0.2577 / Cross valid method: FREE R-VALUE / σ(F): 1.37 / Phase error: 23.7515
Stereochemistry target values: GeoStd + Monomer Library + CDL v1.2
RfactorNum. reflection% reflection
Rfree0.235 497 5.07 %
Rwork0.1975 9302 -
obs0.1994 9799 99.96 %
Solvent computationShrinkage radii: 0.9 Å / VDW probe radii: 1.1 Å / Solvent model: FLAT BULK SOLVENT MODEL
Displacement parametersBiso mean: 52.63 Å2
Refinement stepCycle: LAST / Resolution: 2.5→58.89 Å
ProteinNucleic acidLigandSolventTotal
Num. atoms2115 0 43 62 2220
Refine LS restraints
Refine-IDTypeDev idealNumber
X-RAY DIFFRACTIONf_bond_d0.00192219
X-RAY DIFFRACTIONf_angle_d0.47633007
X-RAY DIFFRACTIONf_chiral_restr0.0438327
X-RAY DIFFRACTIONf_plane_restr0.0038384
X-RAY DIFFRACTIONf_dihedral_angle_d12.9076811
LS refinement shell
Resolution (Å)Rfactor RfreeNum. reflection RfreeRfactor RworkNum. reflection RworkRefine-ID% reflection obs (%)
2.5-2.750.30531190.24332278X-RAY DIFFRACTION100
2.75-3.150.25491410.22552251X-RAY DIFFRACTION100
3.15-3.970.24171130.19472326X-RAY DIFFRACTION99.96
3.97-58.890.20461240.17692447X-RAY DIFFRACTION99.88
Refinement TLS params.

Method: refined / Refine-ID: X-RAY DIFFRACTION

IDL112)L122)L132)L222)L232)L332)S11 (Å °)S12 (Å °)S13 (Å °)S21 (Å °)S22 (Å °)S23 (Å °)S31 (Å °)S32 (Å °)S33 (Å °)T112)T122)T132)T222)T232)T332)Origin x (Å)Origin y (Å)Origin z (Å)
10.775817958450.02266062617171.669311640.579015003063-0.6688079533954.45774652832-0.188731300706-0.4800320721470.623745189020.1073250315490.1885030188250.404110052819-0.711439050822-0.7143345885580.1518366463790.689787413585-0.07998335994980.005023053212930.5037353703-0.07419264594230.409392666876-16.214774155318.80213422375.88186791736
22.361382597881.310134368181.480678825465.364981437110.5604604452422.642579330210.196465444395-0.233508479009-0.257261316850.340402699361-0.192092063177-1.059960459340.1036680204220.122556019507-0.03072988564320.158916235673-0.00862024656802-0.05665331243320.3225365142040.03683754946790.357354129999-15.05633952714.199818771132.10731973783
34.622909901521.149339203920.8894474659914.847046803492.99392823883.434025224290.02478833757160.09210006353750.1986918716590.124337616620.0453622612462-0.03258862307380.0189897168955-0.09731105994110.03444269917520.422439977012-0.0722767901484-0.05908520704020.2526307227560.06668779468330.409287473357-16.723457330537.3648162267-7.08966943671
41.880257504891.68021773611-0.3422541651678.37315960555-0.6359208686050.534164034804-0.1986219106520.171368293818-0.146852521805-0.4259840182350.154240050065-0.553540727081-0.08350295905280.00813128471950.07596737512840.281449448102-0.046965569030.04634383427360.3260425137030.02304619892320.208893134596-16.0578289419.6733782191-7.73245368145
Refinement TLS group

Refine-ID: X-RAY DIFFRACTION / Auth asym-ID: A / Label asym-ID: A

IDRefine TLS-IDSelection detailsAuth seq-IDLabel seq-ID
11chain 'A' and (resid 153 through 192 )153 - 192146 - 180
22chain 'A' and (resid 193 through 279 )193 - 279181 - 267
33chain 'A' and (resid 8 through 70 )8 - 701 - 63
44chain 'A' and (resid 71 through 152 )71 - 15264 - 145

+
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