T. Hunter, Protein kinases and phosphatases: the yin and yang of protein 422 phosphorylation and signaling, Cell, vol.80, pp.225-236, 1995.

S. K. Hanks and T. Hunter, Protein kinases 6. The eukaryotic protein kinase superfamily: 424 kinase (catalytic) domain structure and classification, FASEB J, vol.9, pp.576-596, 1995.

S. Cheek, K. Ginalski, H. Zhang, and N. V. Grishin, A comprehensive update of the 426 sequence and structure classification of kinases, BMC Struct Biol, vol.5, p.6, 2005.

J. A. Hoch, Two-component and phosphorelay signal transduction, Curr Op, vol.428

. Microbiol, , vol.3, pp.165-170, 2000.

A. M. Stock, V. L. Robinson, and P. N. Goudreau, Two-component signal transduction, Annu, vol.430

, Rev Biochem, vol.69, pp.183-215, 2000.

C. C. Zhang, Bacterial signalling involving eukaryotic-type protein kinases, Mol, vol.432

. Microbiol, , vol.20, pp.9-15, 1996.

P. J. Kennelly, Protein kinases and protein phosphatases in prokaryotes: a genomic 434 perspective, FEMS Microbiol Lett, vol.206, pp.1-8, 2002.

N. Kannan, S. S. Taylor, Y. Zhai, J. C. Venter, and G. Manning, Structural and functional 436 diversity of the microbial kinome, Plos Biol, vol.5, p.17, 2007.

C. J. Leonard, L. Aravind, and E. V. Koonin, Novel families of putative protein kinases in 438 bacteria and archaea: evolution of the 'eukaryotic' protein kinase superfamily

, Genome Res, vol.8, pp.1038-1047, 1998.

I. A. Stancik, M. S. ?estak, J. B. Axelson-fisk, M. Franjevic, D. Jers et al.,

, Serine/Threonine protein kinases from Bacteria, Archaea and Eukarya share a 442 common evolutionary origin deeply rooted in the tree of life, J Mol Biol, vol.430, pp.443-470, 2018.

S. Pereira, L. Goss, and J. Dworkin, Eukaryote-like serine/threonine kinases and 445 phosphatases in bacteria, Microbiol Mol Biol Rev, vol.75, pp.192-212, 2011.

K. Burnside and L. Rajagopal, Regulation of prokaryotic gene expression by eukaryotic-447 like enzymes, Curr Op Microbiol, vol.15, pp.125-131, 2012.

D. P. Wright and A. T. Ulijasz, Regulation of transcription by eukaryotic-like serine-449

, threonine kinases and phosphatases in Gram-positive bacterial pathogens

, Virulence, vol.5, pp.863-885, 2014.

J. Dworkin, Ser/Thr phosphorylation as a regulatory mechanism in bacteria, Curr Op, p.452

. Microbiol, , vol.24, pp.47-52, 2015.

S. Manuse, A. Fleurie, L. Zucchini, C. Lesterlin, and C. Grangeasse, Role of eukaryotic-454 like serine/threonine kinases in bacterial cell division and morphogenesis, FEMS, vol.455

, Microbiol Rev, vol.40, pp.41-56, 2016.

M. Janczarek, J. Vinardell, P. Lipa, and M. Kara?, Hanks-type serine/threonine protein 457 kinases and phosphatases in bacteria: roles in signaling and adaptation to various 458 environments, Int J Mol Sci, vol.19, p.2872, 2018.

I. Mijakovic, C. Grangeasse, and K. Turgay, Exploring the diversity of protein 460 modifications: special bacterial phosphorylation systems, FEMS Microbiol Rev, vol.461, pp.398-417, 2016.

D. R. Sherman and C. Grundner, Agents of change -concepts in Mycobacterium 463 tuberculosis Ser/Thr/Tyr phosphosignalling, Mol Microbiol, vol.94, pp.231-241, 2014.

S. T. Cole, R. Brosch, J. Parkhill, T. Garnier, C. Churcher et al., Deciphering 465 the biology of Mycobacterium tuberculosis from the complete genome sequence

, Nature, vol.393, pp.537-544, 1998.

A. Mahajan, C. Yuan, H. Lee, E. Chen, P. Wu et al., Structure and 468 function of the phosphothreonine-specific FHA domain, Sci Signal, vol.1, p.12, 2008.

A. Wehenkel, M. Bellinzoni, M. Graña, R. Durán, A. Villarino et al.,

, Mycobacterial Ser/Thr protein kinases and phosphatases: Physiological roles and 471 therapeutic potential, Biochim Biophys Acta, vol.1784, pp.193-202, 2008.

M. Z. Khan, P. Kaur, and V. K. Nandicoori, Targeting the messengers: Serine/threonine 473 protein kinases as potential targets for antimycobacterial drug development

, Life, vol.70, pp.889-904, 2018.

Y. Av-gay, S. Jamil, and S. J. Drews, Expression and characterization of the 476

, Mycobacterium tuberculosis serine/threonine protein kinase PknB, Infect Immun, vol.477, pp.5676-5682, 1999.

A. E. Greenstein, C. Grundner, N. Echols, L. M. Gay, T. N. Lombana et al., , p.479

, Structure/function studies of Ser/Thr and Tyr protein phosphorylation in 480

, Mycobacterium tuberculosis, J Mol Microbiol Biotechnol, vol.9, pp.167-181, 2005.

J. Chao, D. Wong, X. Zheng, V. Poirier, H. Bach et al., Biochim Biophys, p.482

. Acta, , vol.1804, pp.620-627, 2010.

I. M. Shah, M. Laaberki, D. L. Popham, and J. Dworkin, A eukaryotic-like Ser/Thr kinase 601 signals bacteria to exit dormancy in response to peptidoglycan fragments, Cell, vol.602, pp.486-496, 2008.

S. Prisic, S. Dankwa, D. Schwartz, M. F. Chou, J. W. Locasale et al., Extensive 604 phosphorylation with overlapping specificity by Mycobacterium tuberculosis, p.605

, serine/threonine protein kinases, Proc Natl Acad Sci USA, vol.107, pp.7521-7526, 2010.

S. Fortuin, G. G. Tomazella, N. Nagaraj, S. L. Sampson, G. Van-pittius et al., Soares NC, p.607

, Phosphoproteomics analysis of a clinical Mycobacterium tuberculosis Beijing 608 isolate: expanding the mycobacterial phosphoproteome catalog. Front Microbiol, p.609

X. Carette, J. Platig, D. C. Young, M. Helmel, A. T. Young et al., Multisystem 611 analysis of Mycobacterium tuberculosis reveals kinase-dependent remodeling of the 612 pathogen-environment interface, MBio, vol.9, pp.2333-2350, 2018.

B. Calder, C. Albeldas, J. M. Blackburn, and N. C. Soares, Mass spectrometry offers insight 614 into the role of Ser/Thr/Tyr phosphorylation in the Mycobacteria, Front Microbiol, vol.615, p.32, 2016.

U. Kusebauch, C. Ortega, A. Ollodart, R. S. Rogers, D. R. Sherman et al.,

, Mycobacterium tuberculosis supports protein tyrosine phosphorylation, Proc Natl, vol.618

, Acad Sci USA, vol.111, pp.9265-9270, 2014.

C. M. Kang, D. W. Abbott, S. T. Park, C. C. Dascher, L. C. Cantley et al., The 620

, Mycobacterium tuberculosis serine/threonine kinases PknA and PknB: substrate 621 identification and regulation of cell shape, Genes Dev, vol.19, pp.1692-1704, 2005.

S. N. Nagarajan, S. Upadhyay, Y. Chawla, S. Khan, S. Naz et al., Protein, vol.623

, PknA) of Mycobacterium tuberculosis is independently activated and is 624 critical for growth in vitro and survival of the pathogen in the host, J Biol Chem, vol.625, pp.9626-9645, 2015.

A. Singh, A. Singh, Y. Singh, R. Pine, R. Pine et al., Protein kinase I of 627

, Mycobacterium tuberculosis: cellular localization and expression during infection of 628 macrophage-like cells, Tuberculosis, vol.86, pp.28-33, 2006.

C. C. Boutte, C. E. Baer, K. Papavinasasundaram, W. Liu, M. R. Chase et al.,

, A cytoplasmic peptidoglycan amidase homologue controls mycobacterial cell wall 631 synthesis, eLife, 2016.

O. Turapov, F. Forti, B. Kadhim, D. Ghisotti, J. Sassine et al.,

, Two faces of CwlM, an essential PknB substrate

, Cell Rep, vol.25, pp.57-67, 2018.

P. Plocinski, N. Arora, K. Sarva, E. Blaszczyk, H. Qin et al., Mycobacterium 636 tuberculosis CwsA interacts with CrgA and Wag31, and the CrgA-CwsA complex 637 is involved in peptidoglycan synthesis and cell shape determination, J Bacteriol, vol.638, pp.6398-6409, 2012.

C. L. Gee, K. G. Papavinasasundaram, S. R. Blair, C. E. Baer, A. M. Falick et al., A 640 phosphorylated pseudokinase complex controls cell wall synthesis in Mycobacteria

, Sci Signal, vol.5, p.7, 2012.

C. Roumestand, J. Leiba, N. Galophe, E. Margeat, A. Padilla et al., Structural 643 insight into the Mycobacterium tuberculosis Rv0020c protein and its interaction 644 with the PknB kinase, Structure, vol.19, pp.1525-1534, 2011.

M. Gil, A. Lima, B. Rivera, J. Rossello, E. Urdániz et al., New 646 substrates and interactors of the mycobacterial Serine/Threonine protein kinase 647

, PknG identified by a tailored interactomic approach, J Proteomics, vol.192, pp.321-648, 2019.

A. Parikh, S. K. Verma, S. Khan, B. Prakash, and V. K. Nandicoori, PknB-mediated 650 phosphorylation of a novel substrate

, uridyltransferase, modulates its acetyltransferase activity, J Mol Biol, vol.386, pp.652-451, 2009.

, Phosphorylation of the peptidoglycan synthase PonA1 governs the rate of polar 655 elongation in mycobacteria, PLoS Pathog, vol.11, p.1005010, 2015.

C. Schultz, A. Niebisch, A. Schwaiger, U. Viets, S. Metzger et al.,

, Genetic and biochemical analysis of the serine/threonine protein kinases PknA, p.658

. Pknb, PknG and PknL of Corynebacterium glutamicum: evidence for non-659 essentiality and for phosphorylation of OdhI and FtsZ by multiple kinases, Mol, vol.660

. Microbiol, , vol.74, pp.724-741, 2009.

M. Thakur and P. K. Chakraborti, GTPase activity of mycobacterial FtsZ is impaired due 662 to its transphosphorylation by the eukaryotic-type Ser/Thr kinase, PknA, J Biol, p.663

, Chem, vol.281, pp.40107-40113, 2006.

C. M. Kang, S. Nyayapathy, J. Y. Lee, J. W. Suh, and R. N. Husson, Wag31, a homologue of the 665 cell division protein DivIVA, regulates growth, morphology and polar cell wall 666 synthesis in mycobacteria, Microbiology, vol.154, pp.725-735, 2008.

C. Jani, H. Eoh, J. J. Lee, K. Hamasha, M. B. Sahana et al., Regulation of polar 668 peptidoglycan biosynthesis by Wag31 phosphorylation in mycobacteria, BMC, vol.669

. Microbiol, , vol.10, p.327, 2010.

R. Plocinska, L. Martinez, P. Gorla, E. Pandeeti, K. Sarva et al.,

, Mycobacterium tuberculosis MtrB sensor kinase interactions with FtsI and Wag31 672 proteins reveal a role for MtrB distinct from that regulating MtrA activities, J, vol.673

, Bacteriol, vol.196, pp.4120-4129, 2014.

A. M. Hempel, S. Cantlay, V. Molle, S. Wang, M. J. Naldrett et al., , vol.675

, Ser/Thr protein kinase AfsK regulates polar growth and hyphal branching in the 676 filamentous bacteria Streptomyces, Proc Natl Acad Sci USA, vol.109, pp.2371-677, 2012.

L. Novaková, S. Bezousková, P. Pompach, P. Spidlová, L. Sasková et al.,

, Identification of multiple substrates of the StkP Ser/Thr protein kinase in 680

, Streptococcus pneumoniae, J Bacteriol, vol.192, pp.3629-3638, 2010.

A. Fleurie, C. Cluzel, S. Guiral, C. Freton, F. Galisson et al.,

, Mutational dissection of the S/T-kinase StkP reveals crucial roles in cell division of 683

, Streptococcus pneumoniae, Mol Microbiol, vol.83, pp.746-758, 2012.

G. Saalbach, A. M. Hempel, M. Vigouroux, K. Flärdh, M. J. Buttner et al.,

, Determination of phosphorylation sites in the DivIVA cytoskeletal protein of 686

, Streptomyces coelicolor by targeted LC-MS/MS, J Proteome Res, vol.12, pp.4187-687, 2013.

N. Scherr, S. Honnappa, G. Kunz, P. Mueller, R. Jayachandran et al.,

, Structural basis for the specific inhibition of protein kinase G, a virulence factor of 690

, Mycobacterium tuberculosis, Proc Natl Acad Sci USA, vol.104, pp.12151-12156, 2007.

M. Lisa, M. Gil, G. André-leroux, N. Barilone, R. Durán et al.,

, Molecular basis of the activity and the regulation of the eukaryotic-like S/T protein 693

, kinase PknG from Mycobacterium tuberculosis, Structure, vol.23, pp.1-10, 2015.

S. Cowley, M. Ko, N. Pick, R. Chow, K. J. Downing et al., , vol.695

, Mycobacterium tuberculosis protein serine/threonine kinase PknG is linked to

. Microbiol, , vol.52, pp.1691-1702, 2004.

A. Walburger, A. Koul, G. Ferrari, L. Nguyen, C. Prescianotto-baschong et al.,

, Protein kinase G from pathogenic mycobacteria promotes survival within 700 macrophages, Science, vol.304, pp.1800-1804, 2004.

A. D. Van-der-woude, E. Stoop, M. Stiess, S. Wang, R. Ummels et al., Analysis of SecA2-dependent substrates in Mycobacterium marinum identifies 703 protein kinase G (PknG) as a virulence effector, Cell Microbiol, vol.16, pp.280-295, 2014.

M. Z. Khan, A. Bhaskar, S. Upadhyay, P. Kumari, R. S. Rajmani et al., , p.705

, kinase G confers survival advantage to Mycobacterium tuberculosis during latency-706 like conditions, J Biol Chem, vol.292, pp.16093-16108, 2017.

A. Niebisch, A. Kabus, C. Schultz, B. Weil, and M. Bott, Corynebacterial protein kinase G 708 controls 2-oxoglutarate dehydrogenase activity via the phosphorylation status of the 709 OdhI protein, J Biol Chem, vol.281, pp.12300-12307, 2006.

H. M. O'hare, R. Durán, C. Cerveñansky, M. Bellinzoni, A. M. Wehenkel et al.,

, Regulation of glutamate metabolism by protein kinases in mycobacteria, Mol, vol.712

. Microbiol, , vol.70, pp.1408-1423, 2008.

T. J. Nott, G. Kelly, L. Stach, J. Li, S. Westcott et al., An intramolecular switch 714 regulates phosphoindependent FHA domain interactions in Mycobacterium 715 tuberculosis, Sci Signal, vol.2, p.12, 2009.

M. Ventura, B. Rieck, F. Boldrin, G. Degiacomi, M. Bellinzoni et al., GarA 717 is an essential regulator of metabolism in Mycobacterium tuberculosis, Mol, vol.718

. Microbiol, , vol.90, pp.356-366, 2013.

B. Rieck, G. Degiacomi, M. Zimmermann, A. Cascioferro, F. Boldrin et al.,

, PknG senses amino acid availability to control metabolism and virulence of 721

, Mycobacterium tuberculosis, PLoS Pathog, vol.13, p.1006399, 2017.

P. England, A. Wehenkel, S. Martins, S. Hoos, G. André-leroux et al., The, vol.723

, FHA-containing protein GarA acts as a phosphorylation-dependent molecular 724 switch in mycobacterial signaling, FEBS Lett, vol.583, pp.301-307, 2009.

P. Barthe, C. Roumestand, M. J. Canova, L. Kremer, C. Hurard et al., Dynamic 726 and structural characterization of a bacterial FHA protein reveals a new 727 autoinhibition mechanism, Structure, vol.17, pp.568-578, 2009.

J. Tian, R. Bryk, M. Itoh, M. Suematsu, and C. Nathan, Variant tricarboxylic acid cycle in 729

, Mycobacterium tuberculosis: identification of alpha-ketoglutarate decarboxylase

, Proc Natl Acad Sci USA, vol.102, pp.10670-10675, 2005.

L. De-carvalho, H. Zhao, C. E. Dickinson, N. M. Arango, C. D. Lima et al.,

, Activity-based metabolomic profiling of enzymatic function: Identification of 733

, Rv1248c as a mycobacterial 2-hydroxy-3-oxoadipate synthase, Chem Biol, vol.734, pp.323-332, 2010.

T. Wagner, M. Bellinzoni, A. Wehenkel, H. M. O'hare, and P. M. Alzari, Functional 736 plasticity and allosteric regulation of ?-ketoglutarate decarboxylase in central 737 mycobacterial metabolism, Chem Biol, vol.18, pp.1011-1020, 2011.

T. Wagner, N. Barilone, P. M. Alzari, and M. Bellinzoni, A dual conformation of the post-739 decarboxylation intermediate is associated with distinct enzyme states in 740 mycobacterial KGD (?-ketoglutarate decarboxylase), Biochem J, vol.457, pp.425-741, 2014.

A. Balakrishnan, F. Jordan, and C. F. Nathan, Influence of allosteric regulators on 743 individual steps in the reaction catalyzed by Mycobacterium tuberculosis 2-744 hydroxy-3-oxoadipate synthase, J Biol Chem, vol.288, pp.21688-21702, 2013.

D. Tiwari, R. K. Singh, K. Goswami, S. K. Verma, B. Prakash et al., Key 746 residues in Mycobacterium tuberculosis protein kinase G play a role in regulating 747 kinase activity and survival in the host, J Biol Chem, vol.284, pp.27467-27479, 2009.

M. Wittwer, Q. Luo, V. Kaila, and S. A. Dames, Oxidative unfolding of the rubredoxin 749 domain and the natively disordered N-terminal region regulate the catalytic activity 750 of Mycobacterium tuberculosis protein kinase G, J Biol Chem, vol.291, pp.27062-751, 2016.

N. Bhattacharyya, I. N. Nkumama, Z. Newland-smith, L. Lin, W. Yin et al., An aspartate-specific solute-binding protein regulates protein kinase G activity to 754 control glutamate metabolism in Mycobacteria, MBio, vol.9, p.349, 2018.

T. Alber, Signaling mechanisms of the Mycobacterium tuberculosis receptor Ser/Thr 756 protein kinases, Curr Op Struct Biol, vol.19, pp.650-657, 2009.

A. Ruggiero, A. Ruggiero, D. Simone, P. , D. Simone et al.,

, Bacterial cell division regulation by Ser/Thr kinases: a structural perspective

, Curr Protein Pept Sci, vol.13, pp.756-766, 2012.

J. D. Chao, D. Wong, A. , and Y. , Microbial protein-tyrosine kinases, J Biol Chem, vol.761, pp.9463-9472, 2014.

D. Wong, W. Li, J. D. Chao, P. Zhou, G. Narula et al., , p.763

, PtkA, is required for Mycobacterium tuberculosis growth in macrophages, Sci Rep, vol.764, p.155, 2017.