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4.A.6 The PTS Mannose-Fructose-Sorbose (Man) Family

The Man (PTS splinter group) family is unique in several respects among PTS porter families. (1) It is the only PTS family in which members possess a IID protein; (2) It is the only PTS family in which the IIB constituent is phosphorylated on a histidyl rather than a cysteyl residue. (3) Its porter members usually exhibit broad specificity for a range of sugars, rather than being specific for just one or a few sugars. The mannose porter of E. coli, for example, can transport and phosphorylate glucose, mannose, fructose, glucosamine, N-acetylglucosamine, and N-acteylmannosamine (Plumbridge and Vimr, 1999).

The structure of the E. coli IIAMan domain has been shown to exhibit an α/β doubly wound superfold (Hu et al. 2008). The IIB domain also exhibits an α/β doubly wound superfold, but it is very dissimilar from that of the IIA domain (Orriss et al. 2003). Instead, it has the same topology as phosphoglyceromutase. Since both proteins (IIBMan and PGM) catalyze phosphoryl transfer with a phosphohistidine intermediate, both proteins show a similar distribution of active site residues, and both exhibit similar structures, they are probably homologous. 

Solution structures of complexes between the isolated IIAMan and IIBMan domains of the E. coli mannose EII complex have been solved by NMR (Hu et al. 2008). The complex of wild-type IIAMan and IIBMan is a mixture of two species comprising a productive, phosphoryl transfer competent complex and a non-productive complex with the two active site histidines, His-10 of IIAMan and His-175 of IIBMan, separated by approximately 25Å. Mutation of His-10 to a glutamate to mimic phosphorylation, results in the formation of a single productive complex. The apparent equilibrium dissociation constants for the binding of both wild-type and H10E IIAMan to IIBMan are approximately the same (KD ~0.5 mM). The productive complex can readily accommodate a transition state involving a pentacoordinate phosphoryl group with trigonal bipyramidal geometry bonded to the N-ε2 atom of His-10 and the N-δ1 atom of His-175 with negligible (<0.2 Å) local backbone conformational changes in the immediate vicinity of the active site. The non-productive complex is related to the productive one by an approximately 90 degree rotation and an approximately 37 Å translation of IIBMan relative to IIAMan, leaving the active site His-175 fully exposed to solvent in the non-productive complex (Hu et al. 2008).

IICMan of E. coli has six established transmembrane α-helical spanners while IIDMan has only one with most of the polypeptide chain localized to the periplasm. These two proteins together are required for transport although IICMan is presumed to comprise all or most of the sugar transporting channel.

The generalized reaction catalyzed by members of the Man Family is:

Sugar (out) + PEP (in) → Sugar-P (in) + pyruvate (in).

References associated with 4.A.6 family:

Aké, F.M., P. Joyet, J. Deutscher, and E. Milohanic. (2011). Mutational analysis of glucose transport regulation and glucose-mediated virulence gene repression in Listeria monocytogenes. Mol. Microbiol. 81: 274-293. 21564334
Bidart, G.N., J. Rodríguez-Díaz, V. Monedero, and M.J. Yebra. (2014). A unique gene cluster for the utilization of the mucosal and human milk-associated glycans galacto-N-biose and lacto-N-biose in Lactobacillus casei. Mol. Microbiol. 93: 521-538. 24942885
Bourand, A., M.J. Yebra, G. Boël, A. Mazé, and J. Deutscher. (2013). Utilization of D-ribitol by Lactobacillus casei BL23 requires a mannose-type phosphotransferase system and three catabolic enzymes. J. Bacteriol. 195: 2652-2661. 23564164
Brinkkötter, A., H. Klöss, C. Alpert, and J.W. Lengeler. (2000). Pathways for the utilization of N-acetyl-galactosamine and galactosamine in Escherichia coli. Mol. Microbiol. 37: 125-135. 10931310
Brockmeier, A., M. Skopnik, B. Koch, C. Herrmann, W. Hengstenberg, S. Welti, and K. Scheffzek. (2009). Activity of the Enterococcus faecalis EIIA(gnt) PTS component and its strong interaction with EIIB(gnt). Biochem. Biophys. Res. Commun. 388: 630-636. 19703414
Chaillou, S., P.H. Pouwels, and P.W. Postma. (1999). Transport of D-xylose in Lactobacillus pentosus, Lactobacillus casei, and Lactobacillus plantarum: evidence for a mechanism of facilitated diffusion via the phosphoenolpyruvate:mannose phosphotransferase system. J. Bacteriol. 181: 4768-4773. 10438743
Charrier, V., J. Deutscher, A. Galinier, and I. Martin-Verstraete. (1997). Protein phosphorylation chain of a Bacillus subtilis fructose-specific phosphotransferase system and its participation in regulation of the expression of the lev operon. Biochemistry 36: 1163-1172. 9033408
Cléon, F., J. Habersetzer, F. Alcock, H. Kneuper, P.J. Stansfeld, H. Basit, M.I. Wallace, B.C. Berks, and T. Palmer. (2015). The TatC component of the twin-arginine protein translocase functions as an obligate oligomer. Mol. Microbiol. 98: 111-129. 26112072
Cochu, A., C. Vadeboncoeur, S. Moineau, and M. Frenette. (2003). Genetic and biochemical characterization of the phosphoenolpyruvate:glucose/mannose phosphotransferase system of Streptococcus thermophilus. Appl. Environ. Microbiol. 69: 5423-5432. 12957931
Eimer, E., J. Fröbel, A.S. Blümmel, and M. Müller. (2015). TatE as a Regular Constituent of Bacterial Twin-arginine Protein Translocases. J. Biol. Chem. 290: 29281-29289. 26483541
Gschwind, R.M., G. Gemmecker, M. Leutner, H. Kessler, R. Gutknecht, R. Lanz, K. Flükiger, and B. Erni. (1997). Secondary structure of the IIB domain of the Escherichia coli mannose transporter, a new fold in the class of alpha/beta twisted open-sheet structures. FEBS Lett. 404: 45-50. 9074635
Hu, J., K. Hu, D.C. Williams, Jr, M.E. Komlosh, M. Cai, and G.M. Clore. (2008). Solution NMR structures of productive and non-productive complexes between the A and B domains of the cytoplasmic subunit of the mannose transporter of the Escherichia coli phosphotransferase system. J. Biol. Chem. 283: 11024-11037. 18270202
Huber, F. and B. Erni (1996). Membrane topology of the mannose transporter of Escherichia coli K12. Eur. J. Biochem. 239: 810-817. 8774730
Ishikawa, M., T. Iwamoto, T. Nakamura, A. Doyle, S. Fukumoto, and Y. Yamada. (2011). Pannexin 3 functions as an ER Ca2+ channel, hemichannel, and gap junction to promote osteoblast differentiation. J. Cell Biol. 193: 1257-1274. 21690309
Kim, O.B., H. Richter, T. Zaunmüller, S. Graf, and G. Unden. (2011). Role of secondary transporters and phosphotransferase systems in glucose transport by Oenococcus oeni. J. Bacteriol. 193: 6902-6911. 22020640
Kjos, M., I.F. Nes, and D.B. Diep. (2011). Mechanisms of resistance to bacteriocins targeting the mannose phosphotransferase system. Appl. Environ. Microbiol. 77: 3335-3342. 21421780
Kuzniatsova, L., T.M. Winstone, and R.J. Turner. (2016). Identification of protein-protein interactions between the TatB and TatC subunits of the twin-arginine translocase system and respiratory enzyme specific chaperones. Biochim. Biophys. Acta. 1858: 767-775. 26826271
Lee, Y.H., S. Kim, J.H. Kim, I.S. Bang, I.S. Lee, S.H. Bang, and Y.K. Park. (2013). A phosphotransferase system permease is a novel component of CadC signaling in Salmonella enterica. FEMS Microbiol. Lett. 338: 54-61. 23066934
Manzoor, I., S. Shafeeq, M. Afzal, and O.P. Kuipers. (2015). Fucose-Mediated Transcriptional Activation of the fcs Operon by FcsR in Streptococcus pneumoniae. J. Mol. Microbiol. Biotechnol. 25: 120-128. 26159073
Marion, C., J.M. Stewart, M.F. Tazi, A.M. Burnaugh, C.M. Linke, S.A. Woodiga, and S.J. King. (2012). Streptococcus pneumoniae can utilize multiple sources of hyaluronic acid for growth. Infect. Immun. 80: 1390-1398. 22311922
Martin-Verstraete, I., J. Stülke, A. Klier, and G. Rapoport. (1995). Two different mechanisms mediate catabolite repression of the Bacillus subtilis levanase operon. J. Bacteriol. 177: 6919-6927. 7592486
Miller, K.A., R.S. Phillips, J. Mrázek, and T.R. Hoover. (2013). Salmonella utilizes D-glucosaminate via a mannose family phosphotransferase system permease and associated enzymes. J. Bacteriol. 195: 4057-4066. 23836865
Miller, K.A., R.S. Phillips, P.B. Kilgore, G.L. Smith, and T.R. Hoover. (2015). A Mannose Family Phosphotransferase System Permease and Associated Enzymes Are Required for Utilization of Fructoselysine and Glucoselysine in Salmonella enterica Serovar Typhimurium. J. Bacteriol. 197: 2831-2839. 26100043
Nunn, R.S., Z. Markovic-Housley, J.C. Gènovèsio, K. Flükiger, P.J. Rizkallah, H.N. Jansonius, T. Schirmer and B. Erni (1996). The structure of the IIA domain of the mannose transporter from Escherichia coli at 1.7 Å resolution. J. Mol. Biol. 259: 502-511. 8676384
Orriss, G.L., B. Erni, and T. Schirmer. (2003). Crystal structure of the IIB(Sor) domain of the sorbose permease from Klebsiella pneumoniae solved to 1.75A resolution. J. Mol. Biol. 327: 1111-1119. 12662934
Plumbridge, J. (2015). Regulation of the Utilization of Amino Sugars by Escherichia coli and Bacillus subtilis : Same Genes, Different Control. J. Mol. Microbiol. Biotechnol. 25: 154-167. 26159076
Plumbridge, J. and E. Vimr. (1999). Convergent pathways for utilization of the amino sugars N-acetylglucosamine, N-acetylmannosamine, and N-acetylneuraminic acid by Escherichia coli. J. Bacteriol. 181: 47-54. 9864311
Reinelt, S., B. Koch, M. Hothorn, W. Hengstenberg, S. Welti, and K. Scheffzek. (2009). Structure of the Enterococcus faecalis EIIA(gnt) PTS component. Biochem. Biophys. Res. Commun. 388: 626-629. 19682976
Reizer, J., T.M. Ramseier, A. Reizer and M.H. Saier, Jr. (1996). Novel phosphotransferase genes revealed by bacterial genome analysis: A gene cluster encoding a phosphotransferase system permease and metabolic enzymes concerned with N-acetylgalactosamine metabolism. Microbiol. 142: 231-250.
Rephaeli, A.W. and M.H. Saier, Jr. (1980). Substrate specificity and kinetic characterization of sugar uptake and phosphorylation, catalyzed by the mannose enzyme II of the phosphotransferase system in Salmonella typhimurium. J. Biol. Chem. 255: 8585-8591. 6997301
Rodionov, D.A., P. Hebbeln, A. Eudes, J. ter Beek, I.A. Rodionova, G.B. Erkens, D.J. Slotboom, M.S. Gelfand, A.L. Osterman, A.D. Hanson, and T. Eitinger. (2009). A novel class of modular transporters for vitamins in prokaryotes. J. Bacteriol. 191: 42-51. 18931129
Seip, S., R. Lanz, R. Gutknecht, K. Flükiger, and B. Erni. (1997). The fructose transporter of Bacillus subtilis encoded by the lev operon: backbone assignment and secondary structure of the IIB(Lev) subunit. Eur J Biochem 243: 306-314. 9030753
Stülke, J., I. Martin-Verstraete, V. Charrier, A. Klier, J. Deutscher, and G. Rapoport. (1995). The HPr protein of the phosphotransferase system links induction and catabolite repression of the Bacillus subtilis levanase operon. J. Bacteriol. 177: 6928-6936. 7592487
Wehmeier, U.F., B.M. Wöhrl, and J.W. Lengeler. (1995). Molecular analysis of the phosphoenolpyruvate-dependent L-sorbose: phosphotransferase system from Klebsiella pneumoniae and of its multidomain structure. Mol. Gen. Genet. 246: 610-618. 7700234
Yebra, M.J., A. Veyrat, M.A. Santos, and G. Pérez-Martínez. (2000). Genetics of L-sorbose transport and metabolism in Lactobacillus casei. J. Bacteriol. 182: 155-163. 10613875
Yebra, M.J., V. Monedero, M. Zuniga, J. Deutscher, and G. Perez-Martinez. (2006). Molecular analysis of the glucose-specific phosphoenolpyruvate:sugar phosphotransferase system from Lactobacillus casei and its links with the control of sugar metabolism. Microbiology 152: 95-104. 16385119