GTP plus water mimic ATP in the active site of protein kinase CK2

Nat Struct Biol. 1999 Dec;6(12):1100-3. doi: 10.1038/70033.

Abstract

The structures of the catalytic subunit of protein kinase CK2 from Zea mays complexed with Mg2+ and with analogs of ATP or GTP were determined to 2.2 A resolution. Unlike most other protein kinases, CK2 from various sources shows 'dual-cosubstrate specificity', that is, the ability to efficiently use either ATP or GTP as a cosubstrate. The structures of these complexes demonstrate that water molecules are critical to switch the active site of CK2 from an ATP- to a GTP-compatible state. An understanding of the structural basis of dual-cosubstrate specificity may help in the design of drugs that target CK2 or other kinases with this property.

MeSH terms

  • Adenosine Triphosphate / chemistry
  • Adenosine Triphosphate / metabolism
  • Adenylyl Imidodiphosphate / chemistry
  • Adenylyl Imidodiphosphate / metabolism*
  • Binding Sites
  • Casein Kinase II
  • Catalytic Domain
  • Crystallization
  • Crystallography, X-Ray
  • Guanosine Triphosphate / chemistry
  • Guanosine Triphosphate / metabolism
  • Guanylyl Imidodiphosphate / chemistry
  • Guanylyl Imidodiphosphate / metabolism*
  • Hydrogen Bonding
  • Kinetics
  • Magnesium / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Structure, Secondary
  • Protein-Serine-Threonine Kinases / chemistry*
  • Protein-Serine-Threonine Kinases / metabolism*
  • Substrate Specificity
  • Water / metabolism*
  • Zea mays / enzymology

Substances

  • Water
  • Adenylyl Imidodiphosphate
  • Guanylyl Imidodiphosphate
  • Guanosine Triphosphate
  • Adenosine Triphosphate
  • Casein Kinase II
  • Protein-Serine-Threonine Kinases
  • Magnesium

Associated data

  • PDB/1DAW
  • PDB/1DAY