2H6D

Protein Kinase Domain of the Human 5'-AMP-activated protein kinase catalytic subunit alpha-2 (AMPK alpha-2 chain)

Summary for 2H6D

• Entry DOI: 10.2210/pdb2h6d/pdb
• Related: 2F15
• Descriptor: 5'-AMP-activated protein kinase catalytic subunit alpha-2 (2 entities in total)
• Functional Keywords: atp-binding; cholesterol biosynthesis; fatty acid biosynthesis;kinase; lipid synthesis; nucleotide-binding; phosphorylation; serine/threonine-protein kinase; steroid biosynthesis; sterol biosynthesis; transferase, structural genomics, structural genomics consortium, sgc, signaling protein, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P54646
• Total number of polymer chains: 1
• Total formula weight: 31557.75

Authors

Littler, D.R.,Walker, J.R.,Wybenga-Groot, L.,Newman, E.M.,Butler-Cole, C.,Mackenzie, F.,Finerty, P.J.,Weigelt, J.,Sundstrom, M.,Arrowsmith, C.H.,Edwards, A.M.,Bochkarev, A.,Dhe-Paganon, S.,Structural Genomics Consortium (SGC) (deposition date: 2006-05-31, release date: 2006-06-27, Last modification date: 2023-08-30)

Primary citation

Littler, D.R.,Walker, J.R.,Davis, T.,Wybenga-Groot, L.E.,Finerty, P.J.,Newman, E.,Mackenzie, F.,Dhe-Paganon, S.
A conserved mechanism of autoinhibition for the AMPK kinase domain: ATP-binding site and catalytic loop refolding as a means of regulation.
Acta Crystallogr.,Sect.F, 66:143-151, 2010

PubMed Abstract: 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.

PubMed: 20124709
DOI: 10.1107/S1744309109052543

Experimental method

X-RAY DIFFRACTION (1.85 Å)