Skip to main content
SpringerLink
Log in

Alanine dehydrogenases in mycobacteria

  • Minireview
  • Published:
Journal of Microbiology Aims and scope Submit manuscript

Abstract

Since NAD(H)-dependent L-alanine dehydrogenase (EC 1.1.4.1; Ald) was identified as one of the major antigens present in culture filtrates of Mycobacterium tuberculosis, many studies on the enzyme have been conducted. Ald catalyzes the reversible conversion of pyruvate to alanine with concomitant oxidation of NADH to NAD+ and has a homohexameric quaternary structure. Expression of the ald genes was observed to be strongly upregulated in M. tuberculosis and Mycobacterium smegmatis grown in the presence of alanine. Furthermore, expression of the ald genes in some mycobacteria was observed to increase under respiration-inhibitory conditions such as oxygen-limiting and nutrient-starvation conditions. Upregulation of ald expression by alanine or under respiration-inhibitory conditions is mediated by AldR, a member of the Lrp/AsnC family of transcriptional regulators. Mycobacterial Alds were demonstrated to be the enzymes required for utilization of alanine as a nitrogen source and to help mycobacteria survive under respiration-inhibitory conditions by maintaining cellular NADH/NAD+ homeostasis. Several inhibitors of Ald have been developed, and their application in combination with respiration-inhibitory antitubercular drugs such as Q203 and bedaquiline was recently suggested.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Agren, D., Stehr, M., Berthold, C.L., Kapoor, S., Oehlmann, W., Singh, M., and Schneider, G. 2008. Three-dimensional structures of apo- and holo-L-alanine dehydrogenase from Mycobacterium tuberculosis reveal conformational changes upon coenzyme binding. J. Mol. Biol. 377, 1161–1173.

    Article  CAS  PubMed  Google Scholar 

  • Andersen, A.B., Andersen, P., and Ljungqvist, L. 1992. Structure and function of a 40,000-molecular-weight protein antigen of Mycobacterium tuberculosis. Infect. Immun. 60, 2317–2323.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Berney, M. and Cook, G.M. 2010. Unique flexibility in energy metabolism allows mycobacteria to combat starvation and hypoxia. PLoS One 5, e8614.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Berney, M., Greening, C., Conrad, R., Jacobs, W.R. Jr., and Cook, G.M. 2014. An obligately aerobic soil bacterium activates fermentative hydrogen production to survive reductive stress during hypoxia. Proc. Natl. Acad. Sci. USA 111, 11479–11484.

    Article  CAS  PubMed  Google Scholar 

  • Betts, J.C., Lukey, P.T., Robb, L.C., McAdam, R.A., and Duncan, K. 2002. Evaluation of a nutrient starvation model of Mycobacterium tuberculosis persistence by gene and protein expression profiling. Mol. Microbiol. 43, 717–731.

    Article  CAS  PubMed  Google Scholar 

  • Bhat, S.A., Iqbal, I.K., and Kumar, A. 2016. Imaging the NADH: NAD+ homeostasis for understanding the metabolic response of Mycobacterium to physiologically relevant stresses. Front. Cell. Infect. Microbiol. 6, 145.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Boshoff, H.I. and Barry, C.E. 3rd. 2005. Tuberculosis - metabolism and respiration in the absence of growth. Nat. Rev. Microbiol. 3, 70–80.

    Article  CAS  PubMed  Google Scholar 

  • Boshoff, H.I., Myers, T.G., Copp, B.R., McNeil, M.R., Wilson, M.A., and Barry, C.E. 3rd. 2004. The transcriptional responses of Mycobacterium tuberculosis to inhibitors of metabolism: Novel insights into drug mechanisms of action. J. Biol. Chem. 279, 40174–40184.

    Article  CAS  PubMed  Google Scholar 

  • Chan, K., Knaak, T., Satkamp, L., Humbert, O., Falkow, S., and Ramakrishnan, L. 2002. Complex pattern of Mycobacterium marinum gene expression during long-term granulomatous infection. Proc. Natl. Acad. Sci. USA 99, 3920–3925.

    Article  CAS  PubMed  Google Scholar 

  • Chen, J.M., Alexander, D.C., Behr, M.A., and Liu, J. 2003. Mycobacterium bovis BCG vaccines exhibit defects in alanine and serine catabolism. Infect. Immun. 71, 708–716.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen, S. and Calvo, J.M. 2002. Leucine-induced dissociation of Escherichia coli Lrp hexadecamers to octamers. J. Mol. Biol. 318, 1031–1042.

    Article  CAS  PubMed  Google Scholar 

  • Chen, S., Rosner, M.H., and Calvo, J.M. 2001. Leucine-regulated selfassociation of leucine-responsive regulatory protein (Lrp) from Escherichia coli. J. Mol. Biol. 312, 625–635.

    Article  CAS  PubMed  Google Scholar 

  • Cui, Y., Wang, Q., Stormo, G.D., and Calvo, J.M. 1995. A consensus sequence for binding of Lrp to DNA. J. Bacteriol. 177, 4872–4880.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • de los Rios, S. and Perona, J.J. 2007. Structure of the Escherichia coli leucine-responsive regulatory protein Lrp reveals a novel octameric assembly. J. Mol. Biol. 366, 1589–1602.

    Article  CAS  PubMed  Google Scholar 

  • Delforge, D., Devreese, B., Dieu, M., Delaive, E., Van Beeumen, J., and Remacle, J. 1997. Identification of lysine 74 in the pyruvate binding site of alanine dehydrogenase from Bacillus subtilis. Chemical modification with 2,4,6-trinitrobenzenesulfonic acid, nsuccinimidyl 3-(2-pyridyldithio)propionate, and 5'-(p-(fluorosulfonyl) benzoyl)adenosine. J. Biol. Chem. 272, 2276–2284.

    Article  CAS  PubMed  Google Scholar 

  • Desjardins, C.A., Cohen, K.A., Munsamy, V., Abeel, T., Maharaj, K., Walker, B.J., Shea, T.P., Almeida, D.V., Manson, A.L., Salazar, A., et al. 2016. Genomic and functional analyses of Mycobacterium tuberculosis strains implicate ald in D-cycloserine resistance. Nat. Genet. 48, 544–551.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dey, A., Shree, S., Pandey, S.K., Tripathi, R.P., and Ramachandran, R. 2016. Crystal structure of Mycobacterium tuberculosis H37Rv AldR (Rv2779c), a regulator of the ald gene: DNA binding and identification of small molecule inhibitors. J. Biol. Chem. 291, 11967–11980.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dick, T., Lee, B.H., and Murugasu-Oei, B. 1998. Oxygen depletion induced dormancy in Mycobacterium smegmatis. FEMS Microbiol. Lett. 163, 159–164.

    Article  CAS  PubMed  Google Scholar 

  • Eoh, H. and Rhee, K.Y. 2013. Multifunctional essentiality of succinate metabolism in adaptation to hypoxia in Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 110, 6554–6559.

    Article  PubMed  Google Scholar 

  • Ettema, T.J., Brinkman, A.B., Tani, T.H., Rafferty, J.B., and Van Der Oost, J. 2002. A novel ligand-binding domain involved in regulation of amino acid metabolism in prokaryotes. J. Biol. Chem. 277, 37464–37468.

    Article  CAS  PubMed  Google Scholar 

  • Feng, Z., Caceres, N.E., Sarath, G., and Barletta, R.G. 2002. Mycobacterium smegmatis L-alanine dehydrogenase (Ald) is required for proficient utilization of alanine as a sole nitrogen source and sustained anaerobic growth. J. Bacteriol. 184, 5001–5010.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ferrario, M., Ernsting, B.R., Borst, D.W., Wiese, D.E. 2nd, Blumenthal, R.M., and Matthews, R.G. 1995. The leucine-responsive regulatory protein of Escherichia coli negatively regulates transcription of ompC and micF and positively regulates translation of ompF. J. Bacteriol. 177, 103–113.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Garnier, T., Eiglmeier, K., Camus, J.C., Medina, N., Mansoor, H., Pryor, M., Duthoy, S., Grondin, S., Lacroix, C., Monsempe, C., et al. 2003. The complete genome sequence of Mycobacterium bovis. Proc. Natl. Acad. Sci. USA 100, 7877–7882.

    Article  CAS  PubMed  Google Scholar 

  • Giffin, M.M., Modesti, L., Raab, R.W., Wayne, L.G., and Sohaskey, C.D. 2012. ald of Mycobacterium tuberculosis encodes both the alanine dehydrogenase and the putative glycine dehydrogenase. J. Bacteriol. 194, 1045–1054.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Giffin, M.M., Shi, L., Gennaro, M.L., and Sohaskey, C.D. 2016. Role of alanine dehydrogenase of Mycobacterium tuberculosis during recovery from hypoxic nonreplicating persistence. PLoS One 11, e0155522.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goldman, D.S. 1959. Enzyme systems in the mycobacteria. VII. Purification, properties and mechanism of action of the alanine dehydrogenase. Biochim. Biophys. Acta 34, 527–539.

    CAS  PubMed  Google Scholar 

  • Goldman, D.S. and Wagner, M.J. 1962. Enzyme systems in the mycobacteria. XIII. Glycine dehydrogenase and the glyoxylic acid cycle. Biochim. Biophys. Acta 65, 297–306.

    Article  CAS  PubMed  Google Scholar 

  • Graveline, R., Garneau, P., Martin, C., Mourez, M., Hancock, M.A., Lavoie, R., and Harel, J. 2014. Leucine-responsive regulatory protein Lrp and PapI homologues influence phase variation of CS31A fimbriae. J. Bacteriol. 196, 2944–2953.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Grimshaw, C.E. and Cleland, W.W. 1981. Kinetic mechanism of Bacillus subtilis L-alanine dehydrogenase. Biochemistry 20, 5650–5655.

    Article  CAS  PubMed  Google Scholar 

  • Grimshaw, C.E., Cook, P.F., and Cleland, W.W. 1981. Use of isotope effects and pH studies to determine the chemical mechanism of Bacillus subtilis L-alanine dehydrogenase. Biochemistry 20, 5655–5661.

    Article  CAS  PubMed  Google Scholar 

  • Gupta, R.S., Lo, B., and Son, J. 2018. Phylogenomics and comparative genomic studies robustly support division of the genus Mycobacterium into an emended genus Mycobacterium and four novel genera. Front. Microbiol. 9, 67.

    Article  PubMed  PubMed Central  Google Scholar 

  • Hards, K., Robson, J.R., Berney, M., Shaw, L., Bald, D., Koul, A., Andries, K., and Cook, G.M. 2015. Bactericidal mode of action of bedaquiline. J. Antimicrob. Chemother. 70, 2028–2037.

    CAS  PubMed  Google Scholar 

  • Hart, B.R. and Blumenthal, R.M. 2011. Unexpected coregulator range for the global regulator Lrp of Escherichia coli and Proteus mirabilis. J. Bacteriol. 193, 1054–1064.

    Article  CAS  PubMed  Google Scholar 

  • Hutter, B. and Dick, T. 1998. Increased alanine dehydrogenase activity during dormancy in Mycobacterium smegmatis. FEMS Microbiol. Lett. 167, 7–11.

    Article  CAS  PubMed  Google Scholar 

  • Hutter, B. and Singh, M. 1999. Properties of the 40 kDa antigen of Mycobacterium tuberculosis, a functional L-alanine dehydrogenase. Biochem. J. 343 Pt 3, 669–672.

    Article  Google Scholar 

  • Jeong, J.A., Baek, E.Y., Kim, S.W., Choi, J.S., and Oh, J.I. 2013. Regulation of the ald gene encoding alanine dehydrogenase by AldR in Mycobacterium smegmatis. J. Bacteriol. 195, 3610–3620.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jeong, J.A., Hyun, J., and Oh, J.I. 2015. Regulation mechanism of the ald gene encoding alanine dehydrogenase in Mycobacterium smegmatis and Mycobacterium tuberculosis by the Lrp/AsnC family regulator AldR. J. Bacteriol. 197, 3142–3153.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jeong, J.A., Park, S.W., Yoon, D., Kim, S., Kang, H.Y., and Oh, J.I. 2018. Roles of alanine dehydrogenase and induction of its gene in Mycobacterium smegmatis under respiration-inhibitory conditions. J. Bacteriol. 200, e00152–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jungblut, P.R., Schaible, U.E., Mollenkopf, H.J., Zimny-Arndt, U., Raupach, B., Mattow, J., Halada, P., Lamer, S., Hagens, K., and Kaufmann, S.H. 1999. Comparative proteome analysis of Mycobacterium tuberculosis and Mycobacterium bovis BCG strains: towards functional genomics of microbial pathogens. Mol. Microbiol. 33, 1103–1117.

    Article  CAS  PubMed  Google Scholar 

  • Kana, B.D., Weinstein, E.A., Avarbock, D., Dawes, S.S., Rubin, H., and Mizrahi, V. 2001. Characterization of the cydAB-encoded cytochrome bd oxidase from Mycobacterium smegmatis. J. Bacteriol. 183, 7076–7086.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Keuntje, B., Masepohl, B., and Klipp, W. 1995. Expression of the putA gene encoding proline dehydrogenase from Rhodobacter capsulatus is independent of NtrC regulation but requires an Lrp-like activator protein. J. Bacteriol. 177, 6432–6439.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koike, H., Ishijima, S.A., Clowney, L., and Suzuki, M. 2004. The archaeal feast/famine regulatory protein: potential roles of its assembly forms for regulating transcription. Proc. Natl. Acad. Sci. USA 101, 2840–2845.

    Article  CAS  PubMed  Google Scholar 

  • Koul, A., Vranckx, L., Dhar, N., Gohlmann, H.W., Ozdemir, E., Neefs, J.M., Schulz, M., Lu, P., Mortz, E., McKinney, J.D., et al. 2014. Delayed bactericidal response of Mycobacterium tuberculosis to bedaquiline involves remodelling of bacterial metabolism. Nat. Commun. 5, 3369.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kumarevel, T., Nakano, N., Ponnuraj, K., Gopinath, S.C., Sakamoto, K., Shinkai, A., Kumar, P.K., and Yokoyama, S. 2008. Crystal structure of glutamine receptor protein from Sulfolobus tokodaii strain 7 in complex with its effector L-glutamine: Implications of effector binding in molecular association and DNA binding. Nucleic Acids Res. 36, 4808–4820.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lambert, M.P. and Neuhaus, F.C. 1972. Mechanism of D-cycloserine action: alanine racemase from Escherichia coli W. J. Bacteriol. 110, 978–987.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Leonard, P.M., Smits, S.H., Sedelnikova, S.E., Brinkman, A.B., de Vos, W.M., van der Oost, J., Rice, D.W., and Rafferty, J.B. 2001. Crystal structure of the Lrp-like transcriptional regulator from the archaeon Pyrococcus furiosus. EMBO J. 20, 990–997.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ling, B., Sun, M., Bi, S., Jing, Z., and Liu, Y. 2012. Molecular dynamics simulations of the coenzyme induced conformational changes of Mycobacterium tuberculosis L-alanine dehydrogenase. J. Mol. Graph. Model. 35, 1–10.

    Article  CAS  PubMed  Google Scholar 

  • Ljungqvist, L., Worsaae, A., and Heron, I. 1988. Antibody responses against Mycobacterium tuberculosis in 11 strains of inbred mice: novel monoclonal antibody specificities generated by fusions, using spleens from BALB.B10 and CBA/J mice. Infect. Immun. 56, 1994–1998.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Marasco, R., Varcamonti, M., La Cara, F., Ricca, E., De Felice, M., and Sacco, M. 1994. In vivo footprinting analysis of Lrp binding to the ilvIH promoter region of Escherichia coli. J. Bacteriol. 176, 5197–5201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Matsoso, L.G., Kana, B.D., Crellin, P.K., Lea-Smith, D.J., Pelosi, A., Powell, D., Dawes, S.S., Rubin, H., Coppel, R.L., and Mizrahi, V. 2005. Function of the cytochrome bc 1-aa 3 branch of the respiratory network in mycobacteria and network adaptation occurring in response to its disruption. J. Bacteriol. 187, 6300–6308.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mayuri, Bagchi, G., Das, T.K., and Tyagi, J.S. 2002. Molecular analysis of the dormancy response in Mycobacterium smegmatis: expression analysis of genes encoding the DevR-DevS two-component system, Rv3134c and chaperone alpha-crystallin homologues. FEMS Microbiol. Lett. 211, 231–237.

    CAS  PubMed  Google Scholar 

  • Moraski, G.C., Markley, L.D., Hipskind, P.A., Boshoff, H., Cho, S., Franzblau, S.G., and Miller, M.J. 2011. Advent of imidazo[1,2-a] pyridine-3-carboxamides with potent multi- and extended drug resistant antituberculosis activity. ACS Med. Chem. Lett. 2, 466–470.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nou, X., Braaten, B., Kaltenbach, L., and Low, D.A. 1995. Differential binding of Lrp to two sets of pap DNA binding sites mediated by PapI regulates Pap phase variation in Escherichia coli. EMBO J. 14, 5785–5797.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nou, X., Skinner, B., Braaten, B., Blyn, L., Hirsch, D., and Low, D. 1993. Regulation of pyelonephritis-associated pili phase-variation in Escherichia coli: binding of the PapI and the Lrp regulatory proteins is controlled by DNA methylation. Mol. Microbiol. 7, 545–553.

    Article  CAS  PubMed  Google Scholar 

  • Okamura, H., Yokoyama, K., Koike, H., Yamada, M., Shimowasa, A., Kabasawa, M., Kawashima, T., and Suzuki, M. 2007. A structural code for discriminating between transcription signals revealed by the feast/famine regulatory protein DM1 in complex with ligands. Structure 15, 1325–1338.

    Article  CAS  PubMed  Google Scholar 

  • Park, H.D., Guinn, K.M., Harrell, M.I., Liao, R., Voskuil, M.I., Tompa, M., Schoolnik, G.K., and Sherman, D.R. 2003. Rv3133c/dosR is a transcription factor that mediates the hypoxic response of Mycobacterium tuberculosis. Mol. Microbiol. 48, 833–843.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prosser, G.A. and de Carvalho, L.P. 2013. Metabolomics reveal Dalanine: D-alanine ligase as the target of D-cycloserine in Mycobacterium tuberculosis. ACS Med. Chem. Lett. 4, 1233–1237.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rao, S.P., Alonso, S., Rand, L., Dick, T., and Pethe, K. 2008. The protonmotive force is required for maintaining ATP homeostasis and viability of hypoxic, nonreplicating Mycobacterium tuberculosis. Proc. Natl. Acad. Sci. USA 105, 11945–11950.

    Article  PubMed  Google Scholar 

  • Reddy, M.C., Gokulan, K., Jacobs, W.R. Jr., Ioerger, T.R., and Sacchettini, J.C. 2008. Crystal structure of Mycobacterium tuberculosis LrpA, a leucine-responsive global regulator associated with starvation response. Protein Sci. 17, 159–170.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Reshma, R.S., Saxena, S., Bobesh, K.A., Jeankumar, V.U., Gunda, S., Yogeeswari, P., and Sriram, D. 2016. Design and development of new class of Mycobacterium tuberculosis L-alanine dehydrogenase inhibitors. Bioorg. Med. Chem. 24, 4499–4508.

    Article  CAS  PubMed  Google Scholar 

  • Rosenkrands, I., Slayden, R.A., Crawford, J., Aagaard, C., Barry, C.E. 3rd, and Andersen, P. 2002. Hypoxic response of Mycobacterium tuberculosis studied by metabolic labeling and proteome analysis of cellular and extracellular proteins. J. Bacteriol. 184, 3485–3491.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Russell, D.G. 2007. Who puts the tubercle in tuberculosis? Nat. Rev. Microbiol. 5, 39–47.

    CAS  Google Scholar 

  • Rustad, T.R., Sherrid, A.M., Minch, K.J., and Sherman, D.R. 2009. Hypoxia: a window into Mycobacterium tuberculosis latency. Cell. Microbiol. 11, 1151–1159.

    Article  CAS  PubMed  Google Scholar 

  • Samala, G., Brindha Devi, P., Saxena, S., Gunda, S., Yogeeswari, P., and Sriram, D. 2016. Anti-tubercular activities of 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amine analogues endowed with high activity toward non-replicative Mycobacterium tuberculosis. Bioorg. Med. Chem. 24, 5556–5564.

    Article  CAS  PubMed  Google Scholar 

  • Samala, G., Kakan, S.S., Nallangi, R., Devi, P.B., Sridevi, J.P., Saxena, S., Yogeeswari, P., and Sriram, D. 2014. Investigating structureactivity relationship and mechanism of action of antitubercular 1-(4-chlorophenyl)-4-(4-hydroxy-3-methoxy-5-nitrobenzylidene) pyrazolidine-3,5-dione [CD59]. Int. J. Mycobacteriol. 3, 117–126.

    Article  PubMed  Google Scholar 

  • Saxena, S., Devi, P.B., Soni, V., Yogeeswari, P., and Sriram, D. 2014. Identification of novel inhibitors against Mycobacterium tuberculosis L-alanine dehydrogenase (MTB-AlaDH) through structure-based virtual screening. J. Mol. Graph. Model. 47, 37–43.

    Article  CAS  PubMed  Google Scholar 

  • Saxena, S., Samala, G., Sridevi, J.P., Devi, P.B., Yogeeswari, P., and Sriram, D. 2015. Design and development of novel Mycobacterium tuberculosis L-alanine dehydrogenase inhibitors. Eur. J. Med. Chem. 92, 401–414.

    Article  CAS  PubMed  Google Scholar 

  • Scandurra, G.M., Ryan, A.A., Pinto, R., Britton, W.J., and Triccas, J.A. 2006. Contribution of L-alanine dehydrogenase to in vivo persistence and protective efficacy of the BCG vaccine. Microbiol. Immunol. 50, 805–810.

    Article  CAS  PubMed  Google Scholar 

  • Schnappinger, D., Ehrt, S., Voskuil, M.I., Liu, Y., Mangan, J.A., Monahan, I.M., Dolganov, G., Efron, B., Butcher, P.D., Nathan, C., et al. 2003. Transcriptional adaptation of Mycobacterium tuberculosis within macrophages: insights into the phagosomal environment. J. Exp. Med. 198, 693–704.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Schuffenhauer, G., Schrader, T., and Andreesen, J.R. 1999. Morpholine-induced formation of L-alanine dehydrogenase activity in Mycobacterium strain HE5. Arch. Microbiol. 171, 417–423.

    Article  CAS  PubMed  Google Scholar 

  • Sherman, D.R., Voskuil, M., Schnappinger, D., Liao, R., Harrell, M.I., and Schoolnik, G.K. 2001. Regulation of the Mycobacterium tuberculosis hypoxic response gene encoding alpha-crystallin. Proc. Natl. Acad. Sci. USA 98, 7534–7539.

    Article  CAS  PubMed  Google Scholar 

  • Shrivastava, T., Dey, A., and Ramachandran, R. 2009. Ligand-induced structural transitions, mutational analysis, and ‘open’ quaternary structure of the M. tuberculosis feast/famine regulatory protein (Rv3291c). J. Mol. Biol. 392, 1007–1019.

    Article  CAS  PubMed  Google Scholar 

  • Shrivastava, T. and Ramachandran, R. 2007. Mechanistic insights from the crystal structures of a feast/famine regulatory protein from Mycobacterium tuberculosis H37Rv. Nucleic Acids Res. 35, 7324–7335.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sohaskey, C.D. and Wayne, L.G. 2003. Role of narK2X and narGHJI in hypoxic upregulation of nitrate reduction by Mycobacterium tuberculosis. J. Bacteriol. 185, 7247–7256.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Starck, J., Kallenius, G., Marklund, B.I., Andersson, D.I., and Akerlund, T. 2004. Comparative proteome analysis of Mycobacterium tuberculosis grown under aerobic and anaerobic conditions. Microbiology 150, 3821–3829.

    Article  CAS  PubMed  Google Scholar 

  • Suzuki, M. 2003. The DNA-binding specificity of eubacterial and archaeal FFRPs. Proc. Jpn. Acad. 79B, 213–222.

    Article  Google Scholar 

  • Thaw, P., Sedelnikova, S.E., Muranova, T., Wiese, S., Ayora, S., Alonso, J.C., Brinkman, A.B., Akerboom, J., van der Oost, J., and Rafferty, J.B. 2006. Structural insight into gene transcriptional regulation and effector binding by the Lrp/AsnC family. Nucleic Acids Res. 34, 1439–1449.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tripathi, S.M. and Ramachandran, R. 2008a. Crystal structures of the Mycobacterium tuberculosis secretory antigen alanine dehydrogenase (Rv2780) in apo and ternary complex forms captures “open” and “closed” enzyme conformations. Proteins 72, 1089–1095.

    Article  CAS  PubMed  Google Scholar 

  • Tripathi, S.M. and Ramachandran, R. 2008b. Overexpression, purification, crystallization and preliminary X-ray analysis of Rv-2780 from Mycobacterium tuberculosis H37Rv. Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun. 64, 367–370.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Usha, V., Jayaraman, R., Toro, J.C., Hoffner, S.E., and Das, K.S. 2002. Glycine and alanine dehydrogenase activities are catalyzed by the same protein in Mycobacterium smegmatis: upregulation of both activities under microaerophilic adaptation. Can. J. Microbiol. 48, 7–13.

    Article  CAS  PubMed  Google Scholar 

  • van der Woude, M.W. and Low, D.A. 1994. Leucine-responsive regulatory protein and deoxyadenosine methylase control the phase variation and expression of the sfa and daa pili operons in Escherichia coli. Mol. Microbiol. 11, 605–618.

    Article  PubMed  Google Scholar 

  • Voskuil, M.I., Schnappinger, D., Visconti, K.C., Harrell, M.I., Dolganov, G.M., Sherman, D.R., and Schoolnik, G.K. 2003. Inhibition of respiration by nitric oxide induces a Mycobacterium tuberculosis dormancy program. J. Exp. Med. 198, 705–713.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang, Q. and Calvo, J.M. 1993. Lrp, a global regulatory protein of Escherichia coli, binds co-operatively to multiple sites and activates transcription of ilvIH. J. Mol. Biol. 229, 306–318.

    Article  CAS  PubMed  Google Scholar 

  • Watanabe, S., Zimmermann, M., Goodwin, M.B., Sauer, U., Barry, C.E. 3rd, and Boshoff, H.I. 2011. Fumarate reductase activity maintains an energized membrane in anaerobic Mycobacterium tuberculosis. PLoS Pathog. 7, e1002287.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wayne, L.G. and Hayes, L.G. 1996. An in vitro model for sequential study of shiftdown of Mycobacterium tuberculosis through two stages of nonreplicating persistence. Infect. Immun. 64, 2062–2069.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wayne, L.G. and Lin, K.Y. 1982. Glyoxylate metabolism and adaptation of Mycobacterium tuberculosis to survival under anaerobic conditions. Infect. Immun. 37, 1042–1049.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wayne, L.G. and Sohaskey, C.D. 2001. Nonreplicating persistence of Mycobacterium tuberculosis. Annu. Rev. Microbiol. 55, 139–163.

    Article  CAS  PubMed  Google Scholar 

  • Wiese, D.E. 2nd, Ernsting, B.R., Blumenthal, R.M., and Matthews, R.G. 1997. A nucleoprotein activation complex between the leucine-responsive regulatory protein and DNA upstream of the gltBDF operon in Escherichia coli. J. Mol. Biol. 270, 152–168.

    Article  CAS  PubMed  Google Scholar 

  • Yamada, M., Ishijima, S.A., and Suzuki, M. 2009. Interactions between the archaeal transcription repressor FL11 and its coregulators lysine and arginine. Proteins 74, 520–525.

    Article  CAS  PubMed  Google Scholar 

  • Yang, L., Lin, R.T., and Newman, E.B. 2002. Structure of the Lrpregulated serA promoter of Escherichia coli K-12. Mol. Microbiol. 43, 323–333.

    Article  CAS  PubMed  Google Scholar 

  • Yokoyama, K., Ishijima, S.A., Koike, H., Kurihara, C., Shimowasa, A., Kabasawa, M., Kawashima, T., and Suzuki, M. 2007. Feast/ famine regulation by transcription factor FL11 for the survival of the hyperthermophilic archaeon Pyrococcus OT3. Structure 15, 1542–1554.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Integrated Biological Science, Pusan National University, Busan, 46241, Republic of Korea

    Ji-A Jeong & Jeong-Il Oh

Authors
  1. Ji-A Jeong
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jeong-Il Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jeong-Il Oh.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jeong, JA., Oh, JI. Alanine dehydrogenases in mycobacteria. J Microbiol. 57, 81–92 (2019). https://doi.org/10.1007/s12275-019-8543-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12275-019-8543-7

Keywords

Search

Navigation