title: GTP plus water mimic ATP in the active site of protein kinase CK2.
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.
authors.affiliation: Universität zu Köln, Institut für Biochemie, Zülpicher Strabetae 47, D-50674 Köln, Germany. Karsten.Niefind@uni-koeln.de
authors.forename: K
authors.initials: K
authors.lastname: Niefind
authors.forename: M
authors.initials: M
authors.lastname: Pütter
authors.forename: B
authors.initials: B
authors.lastname: Guerra
authors.forename: O G
authors.initials: OG
authors.lastname: Issinger
authors.forename: D
authors.initials: D
authors.lastname: Schomburg
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000266:Adenylyl Imidodiphosphate / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D047390:Casein Kinase II; D020134:Catalytic Domain; D003460:Crystallization; D018360:Crystallography, X-Ray; D006160:Guanosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D006165:Guanylyl Imidodiphosphate / Q000737:chemistry / Q000378:metabolism*; D006860:Hydrogen Bonding; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000378:metabolism*; D017433:Protein Structure, Secondary; D013379:Substrate Specificity; D014867:Water / Q000378:metabolism*; D003313:Zea mays / Q000201:enzymology
chemical_list: D014867:Water; D000266:Adenylyl Imidodiphosphate; D006165:Guanylyl Imidodiphosphate; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D008274:Magnesium