PDBsum entry 4eal

Transferase

PDB id: 4eal

Contents

Protein chains

92 a.a.

42 a.a.

285 a.a.

Ligands

AMP ×2

Waters ×58

PDB id:

4eal

Name:

Transferase

Title:

Co-crystal of ampk core with atp soaked with amp

Structure:

5'-amp-activated protein kinase catalytic subunit alpha-1. Chain: a. Synonym: ampk subunit alpha-1,acetyl-coa carboxylase kinase,acaca kinase,hydroxymethylglutaryl-coa reductase kinase,hmgcr kinase,tau- protein kinase prkaa1. Ec: 2.7.11.1,2.7.11.27,2.7.11.31,2.7.11.26. Engineered: yes. Other_details: chimera protein of residues 405-479 and residues 540- 559 from 5'-amp-activated protein kinase catalytic subunit alpha-1

Source:

Rattus norvegicus. Rat. Organism_taxid: 10116. Gene: prkaa1, ampk1. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: prkab1. Gene: prkag1.

Resolution:

2.51Å R-factor: 0.235 R-free: 0.277

Authors:

L.Chen,J.Wang,Y.-Y.Zhang,S.F.Yan,D.Neumann,U.Schlattner,Z.-X.Wang,J.- W.Wu

Key ref:

L.Chen et al. (2012). AMP-activated protein kinase undergoes nucleotide-dependent conformational changes. Nat Struct Biol, 19, 716-718. PubMed id: 22659875

Date:

22-Mar-12 Release date: 06-Jun-12

Protein chain

P54645  (AAPK1_RAT) -  5'-AMP-activated protein kinase catalytic subunit alpha-1 from Rattus norvegicus

Seq: 559 a.a.

Struc: 92 a.a.*

Protein chain

P80386  (AAKB1_RAT) -  5'-AMP-activated protein kinase subunit beta-1 from Rattus norvegicus

Seq: 270 a.a.

Struc: 42 a.a.*

Protein chain

P80385  (AAKG1_RAT) -  5'-AMP-activated protein kinase subunit gamma-1 from Rattus norvegicus

Seq: 330 a.a.

Struc: 285 a.a.

* PDB and UniProt seqs differ at 22 residue positions (black crosses)

Enzyme reactions

• Enzyme class 1: Chain A: 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⁺

L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] (Bound ligand (Het Group name = AMP) matches with 85.19% similarity) + ADP + H(+)

L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] (Bound ligand (Het Group name = AMP) matches with 85.19% similarity) + ADP + H(+)

• Enzyme class 2: Chain A: E.C.2.7.11.26 - [tau protein] kinase.
• Reaction:
  1. L-seryl-[tau protein] + ATP = O-phospho-L-seryl-[tau protein] + ADP + H⁺
  2. L-threonyl-[tau protein] + ATP = O-phospho-L-threonyl-[tau protein] + ADP + H⁺

L-seryl-[tau protein] + ATP = O-phospho-L-seryl-[tau protein] (Bound ligand (Het Group name = AMP) matches with 85.19% similarity) + ADP + H(+)

• Enzyme class 3: Chain A: 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⁺

L-seryl-[3-hydroxy-3-methylglutaryl-coenzyme A reductase] + ATP = O-phospho-L-seryl-[3-hydroxy-3-methylglutaryl-coenzyme A reductase] (Bound ligand (Het Group name = AMP) matches with 85.19% similarity) + 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

Nat Struct Biol 19:716-718 (2012)

PubMed id: 22659875

AMP-activated protein kinase undergoes nucleotide-dependent conformational changes.

L.Chen, J.Wang, Y.Y.Zhang, S.F.Yan, D.Neumann, U.Schlattner, Z.X.Wang, J.W.Wu.

ABSTRACT

The energy sensor AMP-activated protein kinase (AMPK) is a heterotrimeric complex that is allosterically activated by AMP binding to the γ subunit. Cocrystal structures of the mammalian AMPK core reveal occlusion of nucleotide-binding site 3 of the γ subunit in the presence of ATP. However, site 3 is occupied in the presence of AMP. Mutagenesis studies indicate that sites 3 and 4 are important for AMPK allosteric activation.