› 4zhx

X-ray diffraction
2.99Å resolution

Novel binding site for allosteric activation of AMPK

Released:
DOI: 10.2210/pdb4zhx/pdb
PDB entry 4zhx coloured by chain, front view.
PDB entry 4zhx coloured by chain, side view.
PDB entry 4zhx coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Structural basis of allosteric and synergistic activation of AMPK by furan-2-phosphonic derivative C2 binding.
Langendorf CG, Ngoei KRW, Scott JW, Ling NXY, Issa SMA, Gorman MA, Parker MW, Sakamoto K, Oakhill JS, Kemp BE
Nat Commun 7 10912 (2016)
PMID: 26952388

Function and Biology Details

Reactions catalysed: 
ATP + a protein = ADP + a phosphoprotein
ATP + [hydroxymethylglutaryl-CoA reductase (NADPH)] = ADP + [hydroxymethylglutaryl-CoA reductase (NADPH)] phosphate
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
hetero trimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-157057 (preferred)
Entry contents:
3 distinct polypeptide molecules
Macromolecules (3 distinct):
5'-AMP-activated protein kinase catalytic subunit alpha-2 Chains: A, C
Molecule details ›
Chains: A, C
Length: 565 amino acids
Theoretical weight: 63.92 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P54646 (Residues: 2-552; Coverage: 100%)
Gene names: AMPK, AMPK2, PRKAA2
Sequence domains:
Structure domains:
5'-AMP-activated protein kinase subunit beta-1 Chains: B, D
Molecule details ›
Chains: B, D
Length: 270 amino acids
Theoretical weight: 30.5 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: Q9Y478 (Residues: 1-270; Coverage: 100%)
Gene names: AMPK, PRKAB1
Sequence domains:
5'-AMP-activated protein kinase subunit gamma-1 Chains: E, F
Molecule details ›
Chains: E, F
Length: 336 amino acids
Theoretical weight: 38.23 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P54619 (Residues: 2-331; Coverage: 100%)
Gene name: PRKAG1
Sequence domains: CBS domain

Ligands and Environments

4 bound ligands:
Ligand 4O7 2 x 4O7
Ligand C1V 2 x C1V
Ligand C2Z 2 x C2Z
Ligand AMP 2 x AMP
2 modified residues:
Ligand TPO 2 x TPO
Ligand SEP 2 x SEP

Experiments and Validation Details

Entry percentile scores
X-ray source: AUSTRALIAN SYNCHROTRON BEAMLINE MX2
Spacegroup: P21
Unit cell:
a: 75.95Å b: 134.24Å c: 141.48Å
α: 90° β: 93.02° γ: 90°
R-values:
R R work R free
0.226 0.225 0.243
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

14 review citations

AMPK in skeletal muscle function and metabolism.
Kjøbsted et al. (2018)
13 more

13 mentions without citation

Multi-Targeted Molecular Effects of Hibiscus sabdariffa Polyphenols: An Opportunity for a Global Approach to Obesity.
Herranz-López et al. (2017)
12 more