An adenylyl cyclase pseudogene in Mycobacterium tuberculosis has a functional ortholog in Mycobacterium avium

Shenoy, AR and Srinivas, A and Mahalingam, M and Visweswariah, SS (2005) An adenylyl cyclase pseudogene in Mycobacterium tuberculosis has a functional ortholog in Mycobacterium avium. In: Biochimie, 87 (6). pp. 557-563.

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Abstract

A number of genes similar to mammalian Class III nucleotide cyclases are found in mycobacteria, and biochemical characterization of some of these proteins has indicated that they code for adenylyl cyclases, with properties similar to the mammalian enzymes. Our earlier bioinformatic analysis had predicted that the Rv1120c gene in Mycobacterium tuberculosis is a pseudogene, while analysis of the genome of Mycobacterium avium indicated the presence of a functional ortholog. We therefore cloned and expressed Rv1120c and its ortholog from M. avium, Ma1120, in Escherichia coli, and find that while the protein from M. tuberculosis is misfolded and found in inclusion bodies, Ma1120 is expressed to high levels as a functional adenylyl cyclase. Sequence analysis of Ma1120 indicates interesting variations in critical amino acids that are known to be important for catalytic activity. Ma1120 is maximally active in the presence of MnATP as substrate $(^a^p^pK_m ~ 400 \mu M)$, and is inhibited by P-site inhibitors ($IC_5_0$ of 2',5'-dideoxy-3'-adenosine triphosphate ~730 nM) and tyrphostins $(IC_5_0 ~ 36 \mu M)$ in a manner similar to the mammalian enzymes. This therefore represents the first Class III cyclase biochemically characterized from M. avium, and the absence of a functional ortholog in M. tuberculosis suggests a unique role for this enzyme in M. avium.

Item Type:	Journal Article
Publication:	Biochimie
Publisher:	Elsevier SAS
Additional Information:	Copyright of this item belongs to Elsevier.
Keywords:	Adenylyl cyclase;Cyclic AMP;Mycobacterium tuberculosis;Mycobacterium avium;Pseudogene;Tyrphostin;P-site inhibitor
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited:	27 Feb 2006
Last Modified:	19 Sep 2010 04:23
URI:	http://eprints.iisc.ac.in/id/eprint/5565

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