Mycobacterium tuberculosis S-adenosyl-l-homocysteine hydrolase is negatively regulated by Ser/Thr phosphorylation.

Rosa Milagros Corrales, Jade Leiba, Martin Cohen-Gonsaud, Virginie Molle, Laurent Kremer

Laboratoire de Dynamique des Interactions Membranaires Normales et Pathologiques, Université Montpellier 2, CNRS, UMR 5235, case 107, Place Eugène Bataillon, 34095 Montpellier Cedex 05, France.

Biochemical and biophysical research communications 2013 Jan 11

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S-Adenosylhomocysteine hydrolase (SahH) is known as an ubiquitous player in methylation-based process that maintains the intracellular S-adenosylhomocysteine (SAH) and S-adenosylmethionine (SAM) equilibrium. Given its crucial role in central metabolism in both eukaryotes and prokaryotes, it is assumed that SahH must be regulated, albeit little is known regarding molecular mechanisms governing its activity. We report here that SahH from Mycobacterium tuberculosis can be phosphorylated by mycobacterial Ser/Thr protein kinases and that phosphorylation negatively affects its enzymatic activity. Mass spectrometric analyses and site-directed mutagenesis identified Thr2 and Thr221 as the two phosphoacceptors. SahH_T2D, SahH_T221D and SahH_T2D/T221D, designed to mimic constitutive phosphorylation, exhibited markedly decreased activity compared to the wild-type enzyme. Both residues are fully conserved in other mycobacterial SahH orthologues, suggesting that SahH phosphorylation on Thr2 and Thr221 may represent a novel and presumably more general mechanism of regulation of the SAH/SAM balance in mycobacteria. Copyright © 2012 Elsevier Inc. All rights reserved.

Citation

Rosa Milagros Corrales, Jade Leiba, Martin Cohen-Gonsaud, Virginie Molle, Laurent Kremer. Mycobacterium tuberculosis S-adenosyl-l-homocysteine hydrolase is negatively regulated by Ser/Thr phosphorylation. Biochemical and biophysical research communications. 2013 Jan 11;430(2):858-64