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4.A.2 The PTS Fructose-Mannitol (Fru) Family

The Fru family is a large and complex family which includes several sequenced fructose, mannose and mannitol-specific porters as well as several putative PTS porters of unknown specificities. The fructose porters of this family phosphorylate fructose on the 1-position. Those of family 4.6 phosphorylate fructose on the 6-position. As is true of other members of the PTS-GFL superfamily, the IIC domains of these permeases probably have a uniform 10 TMS topology (Vastermark and Saier 2016; McCoy et al. 2016; Cao et al. 2011).

The IIA, IIB and IIC domains of the fructose- and mannitol-specific porters are demonstrably homologous. The IIB and IIC domains of the fructose porters are only distantly related to the corresponding domains of the mannitol porters. The IIB and IIC domains of these porters are homologous to those of the Glc family (TC #4.A.1) (Chang et al., 2004). However, the structure of the IIA domain of the mannitol porter of E. coli has been determined, and it proved to possess an α2β2α3 secondary structure, a structure which is very different from the β-sandwich structure of IIAGlc. Further, the IIC domains of the mannitol and fructose porters are almost as dissimilar from each other as they are from the glucose (TC #4.A.1) or lactose (TC #4.A.3) families.

This family belongs to the: PTS-GFL Superfamily.

References associated with 4.A.2 family:

Araki N., Suzuki T., Miyauchi K., Kasai D., Masai E. and Fukuda M. (201). Identification and characterization of uptake systems for glucose and fructose in Rhodococcus jostii RHA1. J Mol Microbiol Biotechnol. 20(3):125-36. 21464575
Benchabane, H., L.A. Lortie, N.D. Buckley, L. Trahan, and M. Frenette. (2002). Inactivation of the Streptococcus mutans fxpC gene confers resistance to xylitol, a caries-preventive natural carbohydrate sweetener. J. Dent. Res. 81: 380-386. 12097428
Cai, L., S. Cai, D. Zhao, J. Wu, L. Wang, X. Liu, M. Li, J. Hou, J. Zhou, J. Liu, J. Han, and H. Xiang. (2014). Analysis of the transcriptional regulator GlpR, promoter elements, and posttranscriptional processing involved in fructose-induced activation of the phosphoenolpyruvate-dependent sugar phosphotransferase system in Haloferax mediterranei. Appl. Environ. Microbiol. 80: 1430-1440. 24334671
Cao, Y., X. Jin, E.J. Levin, H. Huang, Y. Zong, M. Quick, J. Weng, Y. Pan, J. Love, M. Punta, B. Rost, W.A. Hendrickson, J.A. Javitch, K.R. Rajashankar, and M. Zhou. (2011). Crystal structure of a phosphorylation-coupled saccharide transporter. Nature 473: 50-54. 21471968
Chang, A.B., R. Lin, W.K. Studley, C.V. Tran, and M.H. Saier, Jr. (2004). Phylogeny as a guide to structure and function of membrane transport proteins. Mol. Membrane Biol. 21: 171-181. 15204625
Comas, I., F. González-Candelas, and M. Zúñiga. (2008). Unraveling the evolutionary history of the phosphoryl-transfer chain of the phosphoenolpyruvate:phosphotransferase system through phylogenetic analyses and genome context. BMC Evol Biol 8: 147. 18485189
Delobbe, A., H. Chalumeau, and P. Gay. (1975). Existence of two alternative pathways for fructose and sorbitol metabolism in Bacillus subtilis Marburg. Eur J Biochem 51: 503-510. 168069
Gaurivaud, P., F. Laigret, E. Verdin, M. Garnier, and J.M. Bové. (2000). Fructose operon mutants of Spiroplasma citri. Microbiology 146(Pt9): 2229-2236. 10974110
Gay, P. and A. Delobbe. (1977). Fructose transport in Bacillus subtilis. Eur J Biochem 79: 363-373. 200418
Heravi, K.M. and J. Altenbuchner. (2014). Regulation of the Bacillus subtilis mannitol utilization genes: promoter structure and transcriptional activation by the wild-type regulator (MtlR) and its mutants. Microbiology 160: 91-101. 24196428
Jacobson, G.R., C.A. Lee, J.E. Leonard, and M.H. Saier, Jr. (1983). Mannitol-specific enzyme II of the bacterial phosphotransferase system. I. Properties of the purified permease. J. Biol. Chem. 258: 10748-10756. 6350293
Jacobson, G.R., L.E. Tanney, D.M. Kelly, K.B. Palman, and S.B. Corn. (1983). Substrate and phospholipid specificity of the purified mannitol permease of Escherichia coli. J. Cell. Biochem. 23: 231-240. 6427236
Johnson, D.A., S.G. Tetu, K. Phillippy, J. Chen, Q. Ren, and I.T. Paulsen. (2008). High-throughput phenotypic characterization of Pseudomonas aeruginosa membrane transport genes. PLoS Genet 4: e1000211. 18833300
Joyet, P., M. Derkaoui, H. Bouraoui, and J. Deutscher. (2015). PTS-Mediated Regulation of the Transcription Activator MtlR from Different Species: Surprising Differences despite Strong Sequence Conservation. J. Mol. Microbiol. Biotechnol. 25: 94-105. 26159071
Kroon, G.J.A., J. Grötzinger, K. Dijkstra, R.M. Scheek and G.T. Robillard (1993). Backbone assignments and secondary structure of the Escherichia coli enzyme-II mannitol A domain determined by heteronuclear three-dimensional NMR spectroscopy. Prot. Sci. 2: 1331-1341. 8401218
Lee, C.A. and M.H. Saier, Jr. (1983). Mannitol-specific enzyme II of the bacterial phosphotransferase system. III. The nucleotide sequence of the permease gene. J. Biol. Chem. 258: 10761-10767. 6309813
Lee, H.Y., M. Magotra, T.Y. Wong, C. Chakraborty, and J.K. Liu. (2012). ATP-dependent fructose uptake system in Deinococcus radiodurans. Appl. Microbiol. Biotechnol. 93: 1241-1248. 21822900
Leonard, J.E. and M.H. Saier, Jr. (1983). Mannitol-specific enzyme II of the bacterial phosphotransferase system. II. Reconstitution of vectorial transphosphorylation in phospholipid vesicles. J. Biol. Chem. 258: 10757-10760. 6350294
Manayan, R., G. Tenn, H.B. Yee, J.D. Desai, M. Yamada, and M.H. Saier, Jr. (1988). Genetic analyses of the mannitol permease of Escherichia coli: isolation and characterization of a transport-deficient mutant which retains phosphorylation activity. J. Bacteriol. 170: 1290-1296. 3277953
McCoy, J.G., Z. Ren, V. Stanevich, J. Lee, S. Mitra, E.J. Levin, S. Poget, M. Quick, W. Im, and M. Zhou. (2016). The Structure of a Sugar Transporter of the Glucose EIIC Superfamily Provides Insight into the Elevator Mechanism of Membrane Transport. Structure 24: 956-964. 27161976
Nguyen, T.X., M.R. Yen, R.D. Barabote, and M.H. Saier, Jr. (2006). Topological predictions for integral membrane permeases of the phosphoenolpyruvate:sugar phosphotransferase system. J. Mol. Microbiol. Biotechnol. 11: 345-360. 17114898
Patron K., Gilot P., Camiade E. and Mereghetti L. (2015). An homolog of the Frz Phosphoenolpyruvate:carbohydrate phosphoTransferase System of extraintestinal pathogenic Escherichia coli is encoded on a genomic island in specific lineages of Streptococcus agalactiae. Infect Genet Evol. 32:44-50. 25733487
Patron, K., P. Gilot, V. Rong, A. Hiron, L. Mereghetti, and E. Camiade. (2017). Inductors and regulatory properties of the genomic island-associated fru2 metabolic operon of Streptococcus agalactiae. Mol. Microbiol. 103: 678-697. 27870221
Pickl A., Johnsen U. and Schonheit P. (2012). Fructose degradation in the haloarchaeon Haloferax volcanii involves a bacterial type phosphoenolpyruvate-dependent phosphotransferase system, fructose-1-phosphate kinase, and class II fructose-1,6-bisphosphate aldolase. J Bacteriol. 194(12):3088-97. 22493022
Powell, B.S., D.L. Court, T. Inada, Y. Nakamura, V. Michotey, X. Cui, A. Reizer, M.H. Saier, Jr. and J. Reizer (1994). Novel proteins of the phosphotransferase system encoded within the rpoN operon of Escherichia coli. J. Biol. Chem 270: 4822-4839. 7876255
Reizer, J., A. Reizer, and M.H. Saier, Jr. (1995). Novel phosphotransferase system genes revealed by bacterial genome analysis--a gene cluster encoding a unique Enzyme I and the proteins of a fructose-like permease system. Microbiology 141(Pt4): 961-971. 7773398
Reizer, J., I.T. Paulsen, A. Reizer, F. Titgemeyer and M.H. Saier, Jr. (1996). Novel phosphotransferase system genes revealed by bacterial genome analysis: the complete complement of pts genes in Mycoplasma genitalium. Microbial Comp. Genomics. 1: 151-164. 9689210
Reizer, J., S. Bachem, A. Reizer, M. Arnaud, M.H. Saier, Jr., and J. Stülke. (1999). Novel phosphotransferase system genes revealed by genome analysis – the complete complement of PTS proteins encoded within the genome of Bacillus subtilis. Microbiology 145: 3419-3429. 10627040
Reizer, J., V. Michotey, A. Reizer, and M.H. Saier, Jr. (1994). Novel phosphotransferase system genes revealed by bacterial genome analysis: unique, putative fructose- and glucoside-specific systems. Protein. Sci. 3: 440-450. 8019415
Richards, V.P., P. Lang, P.D. Bitar, T. Lefébure, Y.H. Schukken, R.N. Zadoks, and M.J. Stanhope. (2011). Comparative genomics and the role of lateral gene transfer in the evolution of bovine adapted Streptococcus agalactiae. Infect Genet Evol 11: 1263-1275. 21536150
Rouquet, G., G. Porcheron, C. Barra, M. Répérant, N.K. Chanteloup, C. Schouler, and P. Gilot. (2009). A metabolic operon in extraintestinal pathogenic Escherichia coli promotes fitness under stressful conditions and invasion of eukaryotic cells. J. Bacteriol. 191: 4427-4440. 19376853
Sampaio, M.M., F. Chevance, R. Dippel, T. Eppler, A. Schlegel, W. Boos, Y.J. Lu, and C.O. Rock. (2004). Phosphotransferase-mediated transport of the osmolyte 2-O-α-mannosyl-D-glycerate in Escherichia coli occurs by the product of the mngA (hrsA) gene and is regulated by the mngR (farR) gene product acting as repressor. J. Biol. Chem. 279: 5537-5548. 14645248
Shakeri-Garakani, A., A. Brinkkötter, K. Schmid, S. Turgut, and J.W. Lengeler. (2004). The genes and enzymes for the catabolism of galactitol, D-tagatose, and related carbohydrates in Klebsiella oxytoca M5a1 and other enteric bacteria display convergent evolution. Mol. Genet. Genomics 271: 717-728. 15257457
Sugiyama, J.E., S. Mahmoodian and G.R. Jacobson (1991). Membrane topology analysis of Escherichia coli mannitol permease by using a nested-deletion method to create mtlA phoA fusions. Proc. Natl. Acad. Sci. USA 88: 9603-9607. 1946374
Suh, J.Y., J. Iwahara, and G.M. Clore. (2007). Intramolecular domain-domain association/dissociation and phosphoryl transfer in the mannitol transporter of Escherichia coli are not coupled. Proc. Natl. Acad. Sci. USA 104: 3153-3158. 17360622
Sun, T. and J. Altenbuchner. (2010). Characterization of a mannose utilization system in Bacillus subtilis. J. Bacteriol. 192: 2128-2139. 20139185
Tanzer, J.M., A. Thompson, Z.T. Wen, and R.A. Burne. (2006). Streptococcus mutans: fructose transport, xylitol resistance, and virulence. J. Dent. Res. 85: 369-373. 16567561
Van der Heiden, E., M. Delmarcelle, P. Simon, M. Counson, M. Galleni, D.I. Freedberg, J. Thompson, B. Joris, and M.D. Battistel. (2015). Synthesis and Physicochemical Characterization of D-Tagatose-1-Phosphate: The Substrate of the Tagatose-1-Phosphate Kinase in the Phosphotransferase System-Mediated D-Tagatose Catabolic Pathway of Bacillus licheniformis. J. Mol. Microbiol. Biotechnol. 25: 106-119. 26159072
Vastermark, A. and M.H. Saier, Jr. (2016). Time to Stop Holding the Elevator: A New Piece of the Transport Protein Mechanism Puzzle. Structure 24: 845-846. 27276425
Wen, Z.T., C. Browngardt, and R.A. Burne. (2001). Characterization of two operons that encode components of fructose-specific enzyme II of the sugar:phosphotransferase system of Streptococcus mutans. FEMS Microbiol. Lett. 205: 337-342. 11750824