The cAMP binding domain: an ancient signaling module.
cAMP-binding domains from several different proteins were analyzed to determine the properties and interactions of this recognition motif. Systematic computational analyses, including structure-based sequence comparison, surface matching, affinity grid analysis, and analyses of the ligand protein interactions were carried out. These analyses show distinctive roles of the sugar phosphate and the adenine in the cAMP-binding module. We propose that the cAMP-binding regulatory proteins function by providing an allosteric system in which the presence or absence of cAMP produces a substantial structural change through the loss of hydrophobic interactions with the adenine ring and consequent repositioning of the C helix. The modified positioning of the helix in turn is recognized by a protein-binding event, completing the allostery.
Berman
Helen M
HM
Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, 610 Taylor Road, Piscataway, NJ 08854-8087, USA. berman@rcsb.rutgers.edu
Ten Eyck
Lynn F
LF
Goodsell
David S
DS
Haste
Nina M
NM
Kornev
Alexandr
A
Taylor
Susan S
SS
D000595:Amino Acid Sequence; D000242:Cyclic AMP / Q000378:metabolism*; D030562:Databases, Protein; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary / Q000502:physiology; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism; D016415:Sequence Alignment; D020539:Sequence Analysis, Protein; D015398:Signal Transduction / Q000502:physiology*
D011506:Proteins; D000242:Cyclic AMP