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2.A.34 The NhaB Na+:H+ Antiporter (NhaB) Family

NhaB homologues are of 513 to 528 amino acyl residues in length and possess about 12 transmembrane α-helical spanners (TMSs). They exhibit a region with limited sequence similarity to a 46 Kd membrane protein of unknown function from Mycobacterium leprae (spP46838) which is homologous to a member of arsenate resistance pumps of bacteria, archaea and eukaryotes (TC #3.A.4). Only Gram-negative bacterial proteins have been functionally characterized.

The E. coli NhaB is 58% identical to the orthologous Vibrio alginolyticus Na+/H+ antiporter (Pinner et al., 1992). Although the latter protein is predicted to exhibit 10 TMSs, construction of NhaB-phoA fusions led to evidence for a 9 TMS model with the N-terminus in the cytoplasm and the C-terminus in the periplasm (Enomoto et al., 1998). A centrally located aspartyl residue in the 3rd TMS of the Vibrio alginolyticus homologue, conserved in all members of the family, has been shown to be essential for activity (Nakamura et al., 2001). The Klebsiella pneumoniae ortholog has also been studied in some detail, revealing stoichiomentric ratios in the wild type and mutant proteins (Patiño-Ruiz et al. 2017; Patiño-Ruiz et al. 2019).

The generalized transport reaction catalyzed by NhaB of E. coli is:

2 Na+ (in) + 3 H+ (out) ⇌ 2 Na+ (out) + 3 H+ (in)

This family belongs to the: IT Superfamily.

References associated with 2.A.34 family:

Enomoto, H., T. Unemoto, M. Nishibuchi, E. Padan, and T. Nakamura. (1998). Topological study of the Vibrio alginolyticus Na+/H+ antiporter using gene fusions in Escherichia coli cells. Biochim. Biophys. Acta 1370: 77-86. 9518558
Nakamura, T., Y. Fujisaki, H. Enomoto, Y. Nakayama, T. Takabe, N. Yamaguchi, and N. Uozumi. (2001). Residue aspartate-147 from the third transmembrane region of Na+/H+ antiporter NhaB of Vibrio alginolyticus plays a role in its activity. J. Bacteriol. 183: 5762-5767. 11544242
Patiño-Ruiz, M., C. Ganea, K. Fendler, and O. Călinescu. (2017). Competition is the basis of the transport mechanism of the NhaB Na+/H+ exchanger from Klebsiella pneumoniae. PLoS One 12: e0182293. 28750048
Patiño-Ruiz, M., K. Fendler, and O. Călinescu. (2019). Mutation of two key aspartate residues alters stoichiometry of the NhaB Na/H exchanger from Klebsiella pneumoniae. Sci Rep 9: 15390. 31659210
Pinner, E., E. Padan, and S. Schuldiner. (1992). Cloning, sequencing and expression of the NhaB gene, encoding a Na+:H+ antiporter in Escherichia coli. J. Biol. Chem. 267: 11064-11068. 1317851
Pinner, E., E. Padan, and S. Schuldiner. (1994). Kinetic properties of NhaB, a Na+/H+ antiporter from Escherichia coli. J. Biol. Chem. 269: 26274-26279. 7929345
Pinner, E., Y. Kotler, E. Padan, and S. Schuldiner. (1993). Physiological role of nhaB, a specific Na+/H+ antiporter in Escherichia coli. J. Biol. Chem. 268: 1729-1734. 8093613
Radchenko, M.V., R. Waditee, S. Oshimi, M. Fukuhara, T. Takabe, and T. Nakamura. (2006). Cloning, functional expression and primary characterization of Vibrio parahaemolyticus K+/H+ antiporter genes in Escherichia coli. Mol. Microbiol. 59: 651-663. 16390457
Shimamoto, T., K. Inaba, P. Thelen, T. Ishikawa, E.B. Goldberg, M. Tsuda, and T. Tsuchiya. (1994). The NhaB Na+/H+ antiporter is essential for intracellular pH regulation under alkaline conditions in Escherichia coli. J Biochem 116: 285-290. 7822245