Two binary complexes (KAP2-C subunit and cAMP-bound KAP2) were built, to investigate molecular interaction. The binding sites of KAP2 include the acidic sequence motif (Asp73-Glu87), the inhibitor peptide/linker region (Arg93-Val118), and beta barrel of cAMP-binding domains (CBD-A/B). The binding surface on the C subunit anchoring KAP2 extends to the inhibitor binding site at the active site cleft (Glu127-Glu230), Pro243-Ser252 helix and the phosphorylated activation loop (Arg194-Thr201) of the large lobe besides some sites in the small lobe. KAP2 undergoes major conformational changes in comparison of the two complexes above, especially the linker region and Met251 at Arg234- Phe252 helix as an inflexion point of the turnaround. Additionally, the interaction between KAP2 and cAMP concentrates on two catalytic motifs (FGELAL and PRAA) of phosphate binding cassette regions and the cyclic-monophosphate and ribose of cAMP. On the other hand, WAVE1 of BAD complex maybe interacts with the D/D domain of KAP2 by each of three helical motifs (Asn24-Lys46, Pro492-Val514, and Glu525-Glu547). This is helpful for our research of molecular mechanism of PKA and further analysis of BAD complex how to modulate glycolysis and apoptosis.
Protein & Peptide Letters publishes short papers in all important aspects of protein and peptide research, including structural studies, recombinant expression, function, synthesis, enzymology, immunology, molecular modeling, drug design etc. Manuscripts must have a significant element of novelty, timeliness and urgency that merit rapid publication. Reports of crystallisation, and preliminary structure determinations of biologically important proteins are acceptable. Purely theoretical papers are also acceptable provided they provide new insight into the principles of protein/peptide structure and function.