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

A. R. Shenoy, A. Srinivas, M. Mahalingam, S. S. Visweswariah

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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 (appKm ∼ 400 μM), and is inhibited by P-site inhibitors (IC50 of 2′,5′-dideoxy- 3′-adenosine triphosphate ∼730 nM) and tyrphostins (IC50 ∼ 36 μM) 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.

Original languageEnglish (US)
Pages (from-to)557-563
Number of pages7
JournalBiochimie
Volume87
Issue number6
DOIs
StatePublished - Jun 2005
Externally publishedYes

Keywords

  • Adenylyl cyclase
  • Cyclic AMP
  • Mycobacterium avium
  • Mycobacterium tuberculosis
  • P-site inhibitor
  • Pseudogene
  • Tyrphostin

ASJC Scopus subject areas

  • Biochemistry

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