title: Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase.
abstract: The crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase complexed with a 20-amino acid substrate analog inhibitor has been solved and partially refined at 2.7 A resolution to an R factor of 0.212. The magnesium adenosine triphosphate (MgATP) binding site was located by difference Fourier synthesis. The enzyme structure is bilobal with a deep cleft between the lobes. The cleft is filled by MgATP and a portion of the inhibitor peptide. The smaller lobe, consisting mostly of amino-terminal sequence, is associated with nucleotide binding, and its largely antiparallel beta sheet architecture constitutes an unusual nucleotide binding motif. The larger lobe is dominated by helical structure with a single beta sheet at the domain interface. This lobe is primarily involved in peptide binding and catalysis. Residues 40 through 280 constitute a conserved catalytic core that is shared by more than 100 protein kinases. Most of the invariant amino acids in this conserved catalytic core are clustered at the sites of nucleotide binding and catalysis.
authors.affiliation: Department of Chemistry, University of California, San Diego, La Jolla 92093-0654.
authors.forename: D R
authors.initials: DR
authors.lastname: Knighton
authors.forename: J H
authors.initials: JH
authors.lastname: Zheng
authors.forename: L F
authors.initials: LF
authors.lastname: Ten Eyck
authors.forename: V A
authors.initials: VA
authors.lastname: Ashford
authors.forename: N H
authors.initials: NH
authors.lastname: Xuong
authors.forename: S S
authors.initials: SS
authors.lastname: Taylor
authors.forename: J M
authors.initials: JM
authors.lastname: Sowadski
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D003198:Computer Simulation; D005583:Fourier Analysis; D046911:Macromolecular Substances; D051379:Mice; D008958:Models, Molecular; D011494:Protein Kinases / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D014961:X-Ray Diffraction
chemical_list: D046911:Macromolecular Substances; D011994:Recombinant Proteins; D000255:Adenosine Triphosphate; D011494:Protein Kinases