Mycobacterial adenylyl cyclases: biochemical diversity and structural plasticity

Abstract

The conversion of adenine and guanine nucleoside triphosphates to cAMP and cGMP is carried out by nucleotide cyclases, which vary in their primary sequence and are therefore grouped into six classes. The class III enzymes encompass all eukaryotic adenylyl and guanylyl cyclase, and several bacterial and archaebacterial cyclases. Mycobacterial nucleotide cyclases show distinct biochemical properties and domain fusions, and we review here biochemical and structural studies on these enzymes from Mycobacterium tuberculosis and related bacteria. We also present an in silico analysis of nucleotide cyclases found in completely sequenced mycobacterial genomes. It is clear that this group of enzymes demonstrates the tinkering in the class III cyclase domain during evolution, involving subtle structural changes that retain the overall catalytic function and fine tune their activities.