Document Detail

A conserved mechanism of autoinhibition for the AMPK kinase domain: ATP-binding site and catalytic loop refolding as a means of regulation.
MedLine Citation:
PMID:  20124709     Owner:  NLM     Status:  MEDLINE    
The AMP-activated protein kinase (AMPK) is a highly conserved trimeric protein complex that is responsible for energy homeostasis in eukaryotic cells. Here, a 1.9 A resolution crystal structure of the isolated kinase domain from the alpha2 subunit of human AMPK, the first from a multicellular organism, is presented. This human form adopts a catalytically inactive state with distorted ATP-binding and substrate-binding sites. The ATP site is affected by changes in the base of the activation loop, which has moved into an inhibited DFG-out conformation. The substrate-binding site is disturbed by changes within the AMPKalpha2 catalytic loop that further distort the enzyme from a catalytically active form. Similar structural rearrangements have been observed in a yeast AMPK homologue in response to the binding of its auto-inhibitory domain; restructuring of the kinase catalytic loop is therefore a conserved feature of the AMPK protein family and is likely to represent an inhibitory mechanism that is utilized during function.
Dene R Littler; John R Walker; Tara Davis; Leanne E Wybenga-Groot; Patrick J Finerty; Elena Newman; Farell Mackenzie; Sirano Dhe-Paganon
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Publication Detail:
Type:  Journal Article     Date:  2010-01-27
Journal Detail:
Title:  Acta crystallographica. Section F, Structural biology and crystallization communications     Volume:  66     ISSN:  1744-3091     ISO Abbreviation:  Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun.     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-03     Completed Date:  2010-03-08     Revised Date:  2013-05-31    
Medline Journal Info:
Nlm Unique ID:  101226117     Medline TA:  Acta Crystallogr Sect F Struct Biol Cryst Commun     Country:  England    
Other Details:
Languages:  eng     Pagination:  143-51     Citation Subset:  IM    
The Structural Genomics Consortium, University of Toronto, 101 College Street, Toronto, Ontario M5G 1L7, Canada.
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MeSH Terms
AMP-Activated Protein Kinases / chemistry*,  metabolism*
Adenosine Triphosphate / chemistry*,  metabolism*
Amino Acid Sequence
Binding Sites
Crystallography, X-Ray
Models, Molecular
Molecular Sequence Data
Protein Folding*
Protein Structure, Quaternary
Protein Structure, Tertiary
Protein Subunits / chemistry,  metabolism
Sequence Alignment
Reg. No./Substance:
0/Protein Subunits; 56-65-5/Adenosine Triphosphate; EC Protein Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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