Gene Symbol: mtlA
Description: mannitol-specific PTS enzyme: IIA, IIB and IIC components
Alias: ECK3588, JW3573, mtlC
Species: Escherichia coli str. K-12 substr. MG1655

Top Publications

  1. Broos J, Gabellieri E, Biemans Oldehinkel E, Strambini G. Efficient biosynthetic incorporation of tryptophan and indole analogs in an integral membrane protein. Protein Sci. 2003;12:1991-2000 pubmed
    ..In addition, we report here that biosynthetic incorporation of Trp analogs can also be effected with less expensive indole analogs, which in vivo are converted to L-Trp analogs. ..
  2. Vos E, ter Horst R, Poolman B, Broos J. Domain complementation studies reveal residues critical for the activity of the mannitol permease from Escherichia coli. Biochim Biophys Acta. 2009;1788:581-6 pubmed publisher
    ..The involvement of specific residue positions in the oligomeric functioning of a sugar-translocating EII protein has not been presented before. ..
  3. Ramseier T, Saier M. cAMP-cAMP receptor protein complex: five binding sites in the control region of the Escherichia coli mannitol operon. Microbiology. 1995;141 ( Pt 8):1901-7 pubmed
    ..The results serve to identify and define five dissimilar CRP binding sites in a single operon of E. coli. A model for mtl operon transcriptional initiation and repression complexes is presented. ..
  4. Lee C, Jacobson G, Saier M. Plasmid-directed synthesis of enzymes required for D-mannitol transport and utilization in Escherichia coli. Proc Natl Acad Sci U S A. 1981;78:7336-40 pubmed
    ..H., Jr. (1979) J. Biol. Chem. 254, 249-252] that mannitol enzyme II consists of a single type of polypeptide chain that has a Mr of 60,000. The plasmid pLC15-48 DNA was characterized by mapping of restriction endonuclease cleavage sites...
  5. Suh J, Tang C, Cai M, Clore G. Visualization of the phosphorylated active site loop of the cytoplasmic B domain of the mannitol transporter II(Mannitol) of the Escherichia coli phosphotransferase system by NMR spectroscopy and residual dipolar couplings. J Mol Biol. 2005;353:1129-36 pubmed
  6. Jacobson G, Kelly D, Finlay D. The intramembrane topography of the mannitol-specific enzyme II of the Escherichia coli phosphotransferase system. J Biol Chem. 1983;258:2955-9 pubmed
    ..Such an orientation is consistent with the reception and transport roles of the mannitol Enzyme II in E. coli. ..
  7. Lee C, Saier M. Mannitol-specific enzyme II of the bacterial phosphotransferase system. III. The nucleotide sequence of the permease gene. J Biol Chem. 1983;258:10761-7 pubmed
    The nucleotide sequence of the mtlA gene, which codes for the mannitol-specific Enzyme II of the Escherichia coli phosphotransferase system, is presented...
  8. Kuruma Y, Nishiyama K, Shimizu Y, Muller M, Ueda T. Development of a minimal cell-free translation system for the synthesis of presecretory and integral membrane proteins. Biotechnol Prog. 2005;21:1243-51 pubmed
    ..Next, integration of an inner membrane protein (MtlA) into U-INVs was achieved in the presence of only SRP (Ffh) and SR (FtsY)...
  9. Otte S, Scholle A, Turgut S, Lengeler J. Mutations which uncouple transport and phosphorylation in the D-mannitol phosphotransferase system of Escherichia coli K-12 and Klebsiella pneumoniae 1033-5P14. J Bacteriol. 2003;185:2267-76 pubmed
    ..truncated mannitol-specific enzymes II (II(Mtl)) which lacked the IIA(Mtl) or IIBA(Mtl) domain(s), and the mtlA genes originated either from E. coli K-12 or from Klebsiella pneumoniae 1033-5P14...

More Information


  1. Otten R, van Lune F, Dijkstra K, Scheek R. 1H, 13C, and 15N resonance assignments of the phosphorylated enzyme IIB of the mannitol-specific phosphoenolpyruvate-dependent phosphotransferase system of Escherichia coli. J Biomol NMR. 2004;30:461-2 pubmed
  2. Veldhuis G, Broos J, Poolman B, Scheek R. Stoichiometry and substrate affinity of the mannitol transporter, EnzymeIImtl, from Escherichia coli. Biophys J. 2005;89:201-10 pubmed
    ..The dependency could be simulated assuming that >50% of the binding sites were occupied with a ligand that shows an affinity for EnzymeIImtl in the same range as mannitol. ..
  3. Pas H, Robillard G. S-phosphocysteine and phosphohistidine are intermediates in the phosphoenolpyruvate-dependent mannitol transport catalyzed by Escherichia coli EIIMtl. Biochemistry. 1988;27:5835-9 pubmed
    ..The hydrolysis characteristics of the phosphopeptide indicate that Cys 384 is the site of phosphorylation. ..
  4. Davis T, Yamada M, Elgort M, Saier M. Nucleotide sequence of the mannitol (mtl) operon in Escherichia coli. Mol Microbiol. 1988;2:405-12 pubmed
    ..Both the operator-promoter region and the intercistronic region between the mtlA and mtlD genes (encoding the mannitol-specific Enzyme II of the phosphotransferase system and mannitol-1-phosphate ..
  5. Veldhuis G, Hink M, Krasnikov V, van den Bogaart G, Hoeboer J, Visser A, et al. The oligomeric state and stability of the mannitol transporter, EnzymeII(mtl), from Escherichia coli: a fluorescence correlation spectroscopy study. Protein Sci. 2006;15:1977-86 pubmed
  6. Tang C, Iwahara J, Clore G. Visualization of transient encounter complexes in protein-protein association. Nature. 2006;444:383-6 pubmed
    ..Qualitatively similar results are presented for two other protein-protein complexes. ..
  7. Suh J, Iwahara J, Clore G. Intramolecular domain-domain association/dissociation and phosphoryl transfer in the mannitol transporter of Escherichia coli are not coupled. Proc Natl Acad Sci U S A. 2007;104:3153-8 pubmed
  8. Beck K, Wu L, Brunner J, Muller M. Discrimination between SRP- and SecA/SecB-dependent substrates involves selective recognition of nascent chains by SRP and trigger factor. EMBO J. 2000;19:134-43 pubmed vitro, we show that SRP recognizes the first signal anchor sequence of a polytopic membrane protein (MtlA) resulting in cotranslational targeting of MtlA to SecY and phospholipids of the plasma membrane...
  9. Koning R, Keegstra W, Oostergetel G, Schuurman Wolters G, Robillard G, Brisson A. The 5 A projection structure of the transmembrane domain of the mannitol transporter enzyme II. J Mol Biol. 1999;287:845-51 pubmed
    ..Each monomer exhibits six domains of high density which most likely correspond to transmembrane alpha-helices and cytoplasmic loops. ..
  10. Legler P, Cai M, Peterkofsky A, Clore G. Three-dimensional solution structure of the cytoplasmic B domain of the mannitol transporter IImannitol of the Escherichia coli phosphotransferase system. J Biol Chem. 2004;279:39115-21 pubmed
    ..All three proteins utilize a cysteine residue in the nucleophilic attack of a phosphoryl group covalently bound to another protein. ..
  11. Vos E, Bokhove M, Hesp B, Broos J. Structure of the cytoplasmic loop between putative helices II and III of the mannitol permease of Escherichia coli: a tryptophan and 5-fluorotryptophan spectroscopy study. Biochemistry. 2009;48:5284-90 pubmed publisher
    ..The results of this work are in better agreement with a 7 A projection map from a single 2D crystal on which no symmetry was imposed. ..
  12. Jiang W, Wu L, Tomich J, Saier M, Niehaus W. Corrected sequence of the mannitol (mtl) operon in Escherichia coli. Mol Microbiol. 1990;4:2003-6 pubmed
  13. Grisafi P, Scholle A, Sugiyama J, Briggs C, Jacobson G, Lengeler J. Deletion mutants of the Escherichia coli K-12 mannitol permease: dissection of transport-phosphorylation, phospho-exchange, and mannitol-binding activities. J Bacteriol. 1989;171:2719-27 pubmed
    We have constructed a series of deletion mutations of the cloned Escherichia coli K-12 mtlA gene, which encodes the mannitol-specific enzyme II of the phosphoenolpyruvate (PEP)-dependent carbohydrate phosphotransferase system...
  14. Lee C, Fournier M, Beckwith J. Escherichia coli 6S RNA is not essential for growth or protein secretion. J Bacteriol. 1985;161:1156-61 pubmed
    ..Studies of the mutant show that the 6S RNA is not essential for growth or for protein secretion. The gene for the 6S RNA (ssr) maps near serA at 63 min on the E. coli genetic map. ..
  15. Sugiyama J, Mahmoodian S, Jacobson G. Membrane topology analysis of Escherichia coli mannitol permease by using a nested-deletion method to create mtlA-phoA fusions. Proc Natl Acad Sci U S A. 1991;88:9603-7 pubmed
    ..We have used gene fusions between mtlA (encoding the permease) and 'phoA (encoding alkaline phosphatase lacking its signal sequence) to further ..
  16. Kroon G, Grotzinger J, Dijkstra K, Scheek R, Robillard G. Backbone assignments and secondary structure of the Escherichia coli enzyme-II mannitol A domain determined by heteronuclear three-dimensional NMR spectroscopy. Protein Sci. 1993;2:1331-41 pubmed
    ..The resulting secondary structure is considerably different from that reported for IIAglc of E. coli and Bacillus subtilis determined by NMR and X-ray. ..
  17. van Montfort R, Pijning T, Kalk K, Hangyi I, Kouwijzer M, Robillard G, et al. The structure of the Escherichia coli phosphotransferase IIAmannitol reveals a novel fold with two conformations of the active site. Structure. 1998;6:377-88 pubmed
    ..Differences in the stabilisation of the invariant residue Arg17 of HPr by the different IIA proteins might be part of a subtle mechanism to control the hierarchy of carbohydrate utilisation by the bacterium. ..
  18. Yamada Y, Chang Y, Daniels G, Wu L, Tomich J, Yamada M, et al. Insertion of the mannitol permease into the membrane of Escherichia coli. Possible involvement of an N-terminal amphiphilic sequence. J Biol Chem. 1991;266:17863-71 pubmed
    ..Several mtlA-phoA gene fusions encoding fused proteins with N-terminal regions derived from the mannitol permease and C-terminal ..
  19. Boy D, Koch H. Visualization of distinct entities of the SecYEG translocon during translocation and integration of bacterial proteins. Mol Biol Cell. 2009;20:1804-15 pubmed publisher
    ..These results suggest that the assembly or the stability of the bacterial SecYEG translocon is influenced by the substrate that needs to be transported. ..
  20. Wuu J, Swartz J. High yield cell-free production of integral membrane proteins without refolding or detergents. Biochim Biophys Acta. 2008;1778:1237-50 pubmed publisher
    ..synthesis of two complex integral membrane transporters, the tetracycline pump (TetA) and mannitol permease (MtlA), in yields of 570+/-50 microg/mL and 130+/-30 microg/mL of vesicle-associated protein, respectively...
  21. Dijkstra D, Broos J, Lolkema J, Enequist H, Minke W, Robillard G. A fluorescence study of single tryptophan-containing mutants of enzyme IImtl of the Escherichia coli phosphoenolpyruvate-dependent mannitol transport system. Biochemistry. 1996;35:6628-34 pubmed
    ..1991). When mannitol is bound to wild-type EIImtl, an increase in fluorescence emission intensity was observed (Wood, 1988) which can now be attributed primarily to increased fluorescence intensity of the tryptophan at position 30. ..
  22. Boer H, ten Hoeve Duurkens R, Robillard G. Relation between the oligomerization state and the transport and phosphorylation function of the Escherichia coli mannitol transport protein: interaction between mannitol-specific enzyme II monomers studied by complementation of inactive site-directe. Biochemistry. 1996;35:12901-8 pubmed
    ..Thus, only one active A, B, and C domain in the dimer is sufficient for transport and phosphorylation activity, and if all three domains are situated on the same subunit, maximum rates are achieved. ..
  23. Solomon E, Lin E. Mutations affecting the dissimilation of mannitol by Escherichia coli K-12. J Bacteriol. 1972;111:566-74 pubmed
    ..In the mutant defective in the enzyme II complex, mannitol is able to induce the dehydrogenase. Thus, mannitol, rather than its phosphorylated product, seems to be the inducer. ..
  24. Figge R, Ramseier T, Saier M. The mannitol repressor (MtlR) of Escherichia coli. J Bacteriol. 1994;176:840-7 pubmed
    ..5. It is homologous to the product of an open reading frame (URF2D) upstream of the E. coli gapB gene but represents a novel type of transcriptional regulatory protein. ..
  25. Stuart M, Koning R, Oostergetel G, Brisson A. Mechanism of formation of multilayered 2D crystals of the enzyme IIC-mannitol transporter. Biochim Biophys Acta. 2004;1663:108-16 pubmed
    ..This mechanism is inextricably associated with the formation of multilayers. ..
  26. Lengeler J. Nature and properties of hexitol transport systems in Escherichia coli. J Bacteriol. 1975;124:39-47 pubmed
    ..a more restricted inducer specificity, we propose to name the system inducible by D-mannitol and coded by the gene mtlA the D-mannitol transport system, the system inducible by D-glucitol and coded by gutA the D-glucitol transport ..
  27. Vervoort E, Bultema J, Schuurman Wolters G, Geertsma E, Broos J, Poolman B. The first cytoplasmic loop of the mannitol permease from Escherichia coli is accessible for sulfhydryl reagents from the periplasmic side of the membrane. J Mol Biol. 2005;346:733-43 pubmed
    ..These and other results suggest that the predicted loop between TM2 and TM3 may fold back into the membrane and form part of the translocation path. ..
  28. Jacobson G, Lee C, Leonard J, Saier M. Mannitol-specific enzyme II of the bacterial phosphotransferase system. I. Properties of the purified permease. J Biol Chem. 1983;258:10748-56 pubmed
    ..These results show that although the mannitol Enzyme II is an integral membrane protein, a considerable portion of its polypeptide chain must also extend into a hydrophilic environment, presumably the cytoplasm. ..
  29. Postma P, Lengeler J. Phosphoenolpyruvate:carbohydrate phosphotransferase system of bacteria. Microbiol Rev. 1985;49:232-69 pubmed
  30. Suh J, Cai M, Williams D, Clore G. Solution structure of a post-transition state analog of the phosphotransfer reaction between the A and B cytoplasmic domains of the mannitol transporter IIMannitol of the Escherichia coli phosphotransferase system. J Biol Chem. 2006;281:8939-49 pubmed
  31. Cornilescu G, Lee B, Cornilescu C, Wang G, Peterkofsky A, Clore G. Solution structure of the phosphoryl transfer complex between the cytoplasmic A domain of the mannitol transporter IIMannitol and HPr of the Escherichia coli phosphotransferase system. J Biol Chem. 2002;277:42289-98 pubmed
  32. Kornberg H. Routes for fructose utilization by Escherichia coli. J Mol Microbiol Biotechnol. 2001;3:355-9 pubmed
    ..possessing the 3,4,5-D-arabino-hexoseconfiguration but with primary specificity for mannose(manXYZ), mannitol (mtlA) and glucitol (gutA) and which, if over-produced, can transport also fructose...