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Science. 2005 May 13;308(5724):1020-3.

The structure of a pH-sensing mycobacterial adenylyl cyclase holoenzyme.

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  • 1Biochemiezentrum der Universit├Ąt Heidelberg, Im Neuenheimer Feld 328, 69120 Heidelberg, Germany.


Class III adenylyl cyclases contain catalytic and regulatory domains, yet structural insight into their interactions is missing. We show that the mycobacterial adenylyl cyclase Rv1264 is rendered a pH sensor by its N-terminal domain. In the structure of the inhibited state, catalytic and regulatory domains share a large interface involving catalytic residues. In the structure of the active state, the two catalytic domains rotate by 55 degrees to form two catalytic sites at their interface. Two alpha helices serve as molecular switches. Mutagenesis is consistent with a regulatory role of the structural transition, and we suggest that the transition is regulated by pH.

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