[English] 日本語
Yorodumi
- PDB-7m74: ATP-bound AMP-activated protein kinase -

+
Open data


ID or keywords:

Loading...

-
Basic information

Entry
Database: PDB / ID: 7m74
TitleATP-bound AMP-activated protein kinase
Components
  • (5'-AMP-activated protein kinase subunit ...) x 2
  • 5'-AMP-activated protein kinase catalytic subunit alpha-1
  • Fab heavy chainFragment antigen-binding
  • Fab light chainFragment antigen-binding
  • Maltose/maltodextrin ABC transporter substrate-binding protein MalE
  • NanobodySingle-domain antibody
KeywordsSIGNALING PROTEIN / AMPK / activation / ATP-binding
Function / homology
Function and homology information


AMPK inhibits chREBP transcriptional activation activity / Lipophagy / import into nucleus / cAMP-dependent protein kinase regulator activity / nucleotide-activated protein kinase complex / Energy dependent regulation of mTOR by LKB1-AMPK / Carnitine metabolism / protein kinase regulator activity / Activation of PPARGC1A (PGC-1alpha) by phosphorylation / regulation of glycolytic process ...AMPK inhibits chREBP transcriptional activation activity / Lipophagy / import into nucleus / cAMP-dependent protein kinase regulator activity / nucleotide-activated protein kinase complex / Energy dependent regulation of mTOR by LKB1-AMPK / Carnitine metabolism / protein kinase regulator activity / Activation of PPARGC1A (PGC-1alpha) by phosphorylation / regulation of glycolytic process / cAMP-dependent protein kinase activity / Macroautophagy / AMP binding / cellular response to nutrient levels / carbohydrate transmembrane transporter activity / positive regulation of protein kinase activity / Activation of AMPK downstream of NMDARs / Translocation of SLC2A4 (GLUT4) to the plasma membrane / TP53 Regulates Metabolic Genes / ADP binding / fatty acid biosynthetic process / positive regulation of cold-induced thermogenesis / spermatogenesis / Regulation of TP53 Activity through Phosphorylation / periplasmic space / protein kinase activity / protein phosphorylation / positive regulation of gene expression / protein kinase binding / signal transduction / nucleoplasm / ATP binding / membrane / nucleus / cytosol / cytoplasm
Similarity search - Function
Association with the SNF1 complex (ASC) domain / ASC domain superfamily / 5'-AMP-activated protein kinase beta subunit, interaction domain / 5'-AMP-activated protein kinase beta subunit, interation domain / AMP-activated protein kinase, glycogen-binding domain / Glycogen recognition site of AMP-activated protein kinase / CBS domain superfamily / Domain in cystathionine beta-synthase and other proteins. / CBS domain / CBS domain ...Association with the SNF1 complex (ASC) domain / ASC domain superfamily / 5'-AMP-activated protein kinase beta subunit, interaction domain / 5'-AMP-activated protein kinase beta subunit, interation domain / AMP-activated protein kinase, glycogen-binding domain / Glycogen recognition site of AMP-activated protein kinase / CBS domain superfamily / Domain in cystathionine beta-synthase and other proteins. / CBS domain / CBS domain / CBS domain profile. / Maltose/Cyclodextrin ABC transporter, substrate-binding protein / Solute-binding family 1, conserved site / Bacterial extracellular solute-binding proteins, family 1 signature. / Bacterial extracellular solute-binding protein / Bacterial extracellular solute-binding protein / Immunoglobulin E-set / Immunoglobulin-like fold
Similarity search - Domain/homology
alpha-maltose / ADENOSINE-5'-DIPHOSPHATE / ADENOSINE MONOPHOSPHATE / ADENOSINE-5'-TRIPHOSPHATE / Chem-TAK / Maltodextrin-binding protein / 5'-AMP-activated protein kinase subunit beta-2 / 5'-AMP-activated protein kinase subunit gamma-1
Similarity search - Component
Biological speciesHomo sapiens (human)
Escherichia coli (E. coli)
Lama glama (llama)
MethodELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.93 Å
AuthorsYan, Y. / Mukherjee, S. / Harikumar, K.G. / Strutzenberg, T. / Zhou, X.E. / Powell, S.K. / Xu, T. / Sheldon, R. / Lamp, J. / Brunzelle, J.S. ...Yan, Y. / Mukherjee, S. / Harikumar, K.G. / Strutzenberg, T. / Zhou, X.E. / Powell, S.K. / Xu, T. / Sheldon, R. / Lamp, J. / Brunzelle, J.S. / Radziwon, K. / Ellis, A. / Novick, S.J. / Vega, I.E. / Jones, R. / Miller, L.J. / Xu, H.E. / Griffin, P.R. / Kossiakoff, A.A. / Melcher, K.
Funding support United States, 1items
OrganizationGrant numberCountry
National Institutes of Health/National Institute of General Medical Sciences (NIH/NIGMS)R01 GM129436 United States
CitationJournal: Science / Year: 2021
Title: Structure of an AMPK complex in an inactive, ATP-bound state.
Authors: Yan Yan / Somnath Mukherjee / Kaleeckal G Harikumar / Timothy S Strutzenberg / X Edward Zhou / Kelly Suino-Powell / Ting-Hai Xu / Ryan D Sheldon / Jared Lamp / Joseph S Brunzelle / Katarzyna ...Authors: Yan Yan / Somnath Mukherjee / Kaleeckal G Harikumar / Timothy S Strutzenberg / X Edward Zhou / Kelly Suino-Powell / Ting-Hai Xu / Ryan D Sheldon / Jared Lamp / Joseph S Brunzelle / Katarzyna Radziwon / Abigail Ellis / Scott J Novick / Irving E Vega / Russell G Jones / Laurence J Miller / H Eric Xu / Patrick R Griffin / Anthony A Kossiakoff / Karsten Melcher /
Abstract: Adenosine monophosphate (AMP)-activated protein kinase (AMPK) regulates metabolism in response to the cellular energy states. Under energy stress, AMP stabilizes the active AMPK conformation, in ...Adenosine monophosphate (AMP)-activated protein kinase (AMPK) regulates metabolism in response to the cellular energy states. Under energy stress, AMP stabilizes the active AMPK conformation, in which the kinase activation loop (AL) is protected from protein phosphatases, thus keeping the AL in its active, phosphorylated state. At low AMP:ATP (adenosine triphosphate) ratios, ATP inhibits AMPK by increasing AL dynamics and accessibility. We developed conformation-specific antibodies to trap ATP-bound AMPK in a fully inactive, dynamic state and determined its structure at 3.5-angstrom resolution using cryo-electron microscopy. A 180° rotation and 100-angstrom displacement of the kinase domain fully exposes the AL. On the basis of the structure and supporting biophysical data, we propose a multistep mechanism explaining how adenine nucleotides and pharmacological agonists modulate AMPK activity by altering AL phosphorylation and accessibility.
History
DepositionMar 26, 2021Deposition site: RCSB / Processing site: RCSB
Revision 1.0Dec 15, 2021Provider: repository / Type: Initial release
Revision 1.1Dec 22, 2021Group: Database references / Source and taxonomy / Structure summary
Category: entity_name_com / entity_src_gen ...entity_name_com / entity_src_gen / struct_ref / struct_ref_seq / struct_ref_seq_dif
Item: _entity_src_gen.gene_src_common_name / _entity_src_gen.pdbx_gene_src_ncbi_taxonomy_id ..._entity_src_gen.gene_src_common_name / _entity_src_gen.pdbx_gene_src_ncbi_taxonomy_id / _struct_ref.db_code / _struct_ref.db_name / _struct_ref.pdbx_align_begin / _struct_ref.pdbx_db_accession / _struct_ref.pdbx_seq_one_letter_code / _struct_ref_seq.db_align_beg / _struct_ref_seq.db_align_end / _struct_ref_seq.pdbx_db_accession

-
Structure visualization

Movie
  • Deposited structure unit
  • Imaged by Jmol
  • Download
  • Superimposition on EM map
  • EMDB-23708
  • Imaged by UCSF Chimera
  • Download
Movie viewer
Structure viewerMolecule:
MolmilJmol/JSmol

Downloads & links

-
Assembly

Deposited unit
A: 5'-AMP-activated protein kinase catalytic subunit alpha-1
B: 5'-AMP-activated protein kinase subunit beta-2
G: 5'-AMP-activated protein kinase subunit gamma-1
M: Maltose/maltodextrin ABC transporter substrate-binding protein MalE
L: Fab light chain
H: Fab heavy chain
N: Nanobody
hetero molecules


Theoretical massNumber of molelcules
Total (without water)216,49312
Polymers214,4707
Non-polymers2,0235
Water0
1


  • Idetical with deposited unit
  • defined by author
  • Evidence: gel filtration
TypeNameSymmetry operationNumber
identity operation1_5551

-
Components

-
Protein , 2 types, 2 molecules AM

#1: Protein 5'-AMP-activated protein kinase catalytic subunit alpha-1


Mass: 56004.395 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PRKAA1, AMPK1 / Production host: Spodoptera frugiperda (fall armyworm)
References: non-specific serine/threonine protein kinase, [acetyl-CoA carboxylase] kinase, [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase, tau-protein kinase
#4: Protein Maltose/maltodextrin ABC transporter substrate-binding protein MalE


Mass: 40827.125 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Escherichia coli (E. coli) / Gene: malE, GRW33_05015 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: A0A6D0N546

-
5'-AMP-activated protein kinase subunit ... , 2 types, 2 molecules BG

#2: Protein 5'-AMP-activated protein kinase subunit beta-2 / AMPK subunit beta-2


Mass: 22384.650 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PRKAB2 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: O43741
#3: Protein 5'-AMP-activated protein kinase subunit gamma-1 / AMPKg


Mass: 34833.359 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Gene: PRKAG1 / Production host: Spodoptera frugiperda (fall armyworm) / References: UniProt: P54619

-
Antibody , 3 types, 3 molecules LHN

#5: Antibody Fab light chain / Fragment antigen-binding


Mass: 22794.248 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli)
#6: Antibody Fab heavy chain / Fragment antigen-binding


Mass: 24466.369 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Homo sapiens (human) / Production host: Escherichia coli (E. coli)
#7: Antibody Nanobody / Single-domain antibody


Mass: 13159.438 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Source: (gene. exp.) Lama glama (llama) / Production host: Escherichia coli (E. coli)

-
Sugars , 1 types, 1 molecules

#8: Polysaccharide alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranose


Type: oligosaccharide, Oligosaccharide / Class: Nutrient / Mass: 342.297 Da / Num. of mol.: 1
Source method: isolated from a genetically manipulated source
Details: oligosaccharide / References: alpha-maltose
DescriptorTypeProgram
DGlcpa1-4DGlcpa1-ROHGlycam Condensed SequenceGMML 1.0
WURCS=2.0/1,2,1/[a2122h-1a_1-5]/1-1/a4-b1WURCSPDB2Glycan 1.1.0
[][a-D-Glcp]{[(4+1)][a-D-Glcp]{}}LINUCSPDB-CARE

-
Non-polymers , 4 types, 4 molecules

#9: Chemical ChemComp-TAK / 6-[4-(2-piperidin-1-ylethoxy)phenyl]-3-pyridin-4-ylpyrazolo[1,5-a]pyrimidine / Dorsomorphin


Mass: 399.488 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C24H25N5O / Feature type: SUBJECT OF INVESTIGATION
#10: Chemical ChemComp-ATP / ADENOSINE-5'-TRIPHOSPHATE / Adenosine triphosphate


Mass: 507.181 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C10H16N5O13P3 / Comment: ATP, energy-carrying molecule*YM
#11: Chemical ChemComp-ADP / ADENOSINE-5'-DIPHOSPHATE / Adenosine diphosphate


Mass: 427.201 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C10H15N5O10P2 / Comment: ADP, energy-carrying molecule*YM
#12: Chemical ChemComp-AMP / ADENOSINE MONOPHOSPHATE / Adenosine monophosphate


Mass: 347.221 Da / Num. of mol.: 1 / Source method: obtained synthetically / Formula: C10H14N5O7P / Comment: AMP*YM

-
Details

Has ligand of interestY

-
Experimental details

-
Experiment

ExperimentMethod: ELECTRON MICROSCOPY
EM experimentAggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction

-
Sample preparation

ComponentName: MBP-fused ATP bound AMPK in complex with C-compound stabilized by Fab and a nanobody
Type: COMPLEX / Entity ID: #1-#7 / Source: RECOMBINANT
Source (natural)Organism: Homo sapiens (human)
Source (recombinant)Organism: Spodoptera frugiperda (fall armyworm)
Buffer solutionpH: 8
SpecimenEmbedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES
Specimen supportGrid material: GOLD / Grid mesh size: 200 divisions/in. / Grid type: Quantifoil R1.2/1.3
VitrificationCryogen name: ETHANE

-
Electron microscopy imaging

Experimental equipment
Model: Titan Krios / Image courtesy: FEI Company
MicroscopyModel: FEI TITAN KRIOS
Electron gunElectron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM
Electron lensMode: BRIGHT FIELDBright-field microscopy / Cs: 2.7 mm / Alignment procedure: COMA FREE
Specimen holderCryogen: NITROGEN
Image recordingElectron dose: 66 e/Å2 / Film or detector model: GATAN K3 (6k x 4k)

-
Processing

SoftwareName: PHENIX / Version: 1.13_2998: / Classification: refinement
EM software
IDNameCategory
2SerialEMimage acquisition
4CTFFINDCTF correction
CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Particle selectionNum. of particles selected: 3918314
3D reconstructionResolution: 3.93 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 569379 / Symmetry type: POINT

+
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