Sci. STKE, 17 May 2005
BIOCHEMISTRY pH Makes the Switch
Adenylyl cyclases (ACs) synthesize the second messenger cyclic AMP (cAMP). Tews et al. have characterized an AC from Mycobacterium tuberculosis that produces cAMP in a pH-dependent manner. The enzyme consists of two complementary monomers, and high-resolution structures show that interaction between the catalytic and regulatory domains prevents formation of the active site in the inhibited (high pH) state. Two molecular switch regions mediate structural rearrangement of the catalytic domains so that they are positioned to form the active site at their interface. Mutagenesis results support the idea that a pH-dependent structural transition regulates activity.
I. Tews, F. Findeisen, I. Sinning, A. Schultz, J. E. Schultz, J. U. Linder, The structure of a pH-sensing mycobacterial adenylyl cyclase holoenzyme. Science 308, 1020-1023 (2005). [Abstract] [Full Text]
Citation: pH Makes the Switch. Sci. STKE 2005, tw193 (2005).
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