PDBsum entry 2h6d

Signaling protein,transferase

PDB id: 2h6d

Contents

Protein chain

256 a.a. *

Waters ×164

* Residue conservation analysis

PDB id:

2h6d

Name:

Signaling protein,transferase

Title:

Protein kinase domain of the human 5'-amp-activated protein kinase catalytic subunit alpha-2 (ampk alpha-2 chain)

Structure:

5'-amp-activated protein kinase catalytic subunit alpha-2. Chain: a. Fragment: kinase domain. Synonym: ampk alpha-2 chain. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: prkaa2, ampk, ampk2. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.

Resolution:

1.85Å R-factor: 0.190 R-free: 0.227

Authors:

D.R.Littler,J.R.Walker,L.Wybenga-Groot,E.M.Newman,C.Butler-Cole, F.Mackenzie,P.J.Finerty,J.Weigelt,M.Sundstrom,C.H.Arrowsmith, A.M.Edwards,A.Bochkarev,S.Dhe-Paganon,Structural Genomics Consortium (Sgc)

Key ref:

D.R.Littler et al. (2010). 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 Struct Biol Cryst Commun, 66, 143-151. PubMed id: 20124709

Date:

31-May-06 Release date: 27-Jun-06

Protein chain

P54646  (AAPK2_HUMAN) -  5'-AMP-activated protein kinase catalytic subunit alpha-2 from Homo sapiens

Seq: 552 a.a.

Struc: 256 a.a.

Enzyme reactions

• Enzyme class 2: E.C.2.7.11.1 - non-specific serine/threonine protein kinase.
• Reaction:
  1. L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + H⁺
  2. L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + ADP + H⁺
• Enzyme class 3: E.C.2.7.11.31 - [hydroxymethylglutaryl-CoA reductase (NADPH)] kinase.
• Reaction: L-seryl-[3-hydroxy-3-methylglutaryl-coenzyme A reductase] + ATP = O-phospho-L-seryl-[3-hydroxy-3-methylglutaryl-coenzyme A reductase] + ADP + H⁺

Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

reference

Acta Crystallogr Sect F Struct Biol Cryst Commun 66:143-151 (2010)

PubMed id: 20124709

A conserved mechanism of autoinhibition for the AMPK kinase domain: ATP-binding site and catalytic loop refolding as a means of regulation.

D.R.Littler, J.R.Walker, T.Davis, L.E.Wybenga-Groot, P.J.Finerty, E.Newman, F.Mackenzie, S.Dhe-Paganon.

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.