Figure 4.

Interfacial mutations in adenylate cyclase and sGC that modulate enzyme activity underscore the key role of the heterodimeric interface for catalysis. We mapped AC and sGC mutations on the structures of the inactive αβGC heterodimer (A and B; PDB entry 4NI2) and the modeled active structure of αβGC (C and D). The model for the active conformation was generated with SWISSMODEL⁶⁷ by using active adenylate cyclase (PDB entry 1CJU) as a template. Residues that affect sGC or AC activity map to two regions of the αβGC heterodimer: (i) the interfacial hydrogen bond network among sGC residues αGC Cys595, αGC Glu526, and βGC Thr 474 (indicated by dashed green lines) and (ii) the sGC flap region (βGC Met537) or the region interacting with the flap in the partner subunit (αGC Asp514). Panels B and D are close-up views of panels A and C, respectively.