The structure of a CAP-DNA complex having two cAMP molecules bound to each monomer.
The 2.2 A resolution crystal structure of the Escherichia coli catabolite gene activator protein (CAP) complexed with cAMP and a 46-bp DNA fragment reveals a second cAMP molecule bound to each protein monomer. The second cAMP is in the syn conformation and is located on the DNA binding domain interacting with the helix-turn-helix, a beta-hairpin from the regulatory domain and the DNA (via water molecules). The presence of this second cAMP site resolves the apparent discrepancy between the NMR and x-ray data on the conformation of cAMP, and explains the cAMP concentration-dependent behaviors of the protein. In addition, this site's close proximity to mutations affecting transcriptional activation and its water-mediated interactions with a DNA recognition residue (E181) and DNA raise the possibility that this site has biological relevance.
Passner
J M
JM
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06511, USA.
Steitz
T A
TA
D000242:Cyclic AMP / Q000378:metabolism*; D002373:Cyclic AMP Receptor Protein / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011485:Protein Binding
D002373:Cyclic AMP Receptor Protein; D004268:DNA-Binding Proteins; D004247:DNA; D000242:Cyclic AMP