title: Regulatory subunit of protein kinase A: structure of deletion mutant with cAMP binding domains.
abstract: In the molecular scheme of living organisms, adenosine 3',5'-monophosphate (cyclic AMP or cAMP) has been a universal second messenger. In eukaryotic cells, the primary receptors for cAMP are the regulatory subunits of cAMP-dependent protein kinase. The crystal structure of a 1-91 deletion mutant of the type I alpha regulatory subunit was refined to 2.8 A resolution. Each of the two tandem cAMP binding domains provides an extensive network of hydrogen bonds that buries the cyclic phosphate and the ribose between two beta strands that are linked by a short alpha helix. Each adenine base stacks against an aromatic ring that lies outside the beta barrel. This structure provides a molecular basis for understanding how cAMP binds cooperatively to its receptor protein, thus mediating activation of the kinase.
authors.affiliation: Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla 92093-0654, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Su
authors.forename: W R
authors.initials: WR
authors.lastname: Dostmann
authors.forename: F W
authors.initials: FW
authors.lastname: Herberg
authors.forename: K
authors.initials: K
authors.lastname: Durick
authors.forename: N H
authors.initials: NH
authors.lastname: Xuong
authors.forename: L
authors.initials: L
authors.lastname: Ten Eyck
authors.forename: S S
authors.initials: SS
authors.lastname: Taylor
authors.forename: K I
authors.initials: KI
authors.lastname: Varughese
mesh_terms: D000345:Affinity Labels; D000595:Amino Acid Sequence; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D003196:Computer Graphics; D003460:Crystallization; D018360:Crystallography, X-Ray; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000737:chemistry*; D004789:Enzyme Activation; D006860:Hydrogen Bonding; D047908:Intracellular Signaling Peptides and Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D017510:Protein Folding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D000345:Affinity Labels; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; C015482:protein kinase modulator; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases