Transporter nucleotide binding domain

Kerr, I.D. (2002) Structure and association of ATP-binding cassette transporter nucleotide-binding domains. Biochimica et Biophysica Acta, 1561 (1), 47-64. 

The phosphorylation and nucleotide binding domains. The phosphorylation domain contains the phosphate acceptor Asp351, that is phos-phorylated by ATP during Ca " " transport [45,80,87,94,95]. Site-specific... 

Fig. 8. Mutagenesis of the predicted ATP binding site. ATP is shown in proximity to amino acids in four loops predicted to form the ATP binding site in the nucleotide binding domain [49,134] and a fifth loop representing the phosphorylation site at Asp351 [97], Mutations and the corresponding Ca transport activity of the mutants relative to wild-type are indicated. From Clarke et al. [103).

The ABC transporters are products of one of the largest gene superfamilies. Each consists of two cytoplasmic nucleotide-binding domains (NBDs) and two transmembrane domains (TMDs). The NBDs are highly conserved across the ABC family and contain motifs typical of ATP-binding sites, whereas the TMD structures vary, probably because they are adapted to the wide variety of substrates. In eukaryotes the C-terminal of each NBD is linked to a TMD. In some cases the functional unit is (NBD-TMD)2 and, in others, the first TMD is covalently linked to the second NBD. 

Nucleotide binding domain or ATP-binding cassette (ABC transporters)... 

All ABC transporters have two nucleotide-binding domains (NBDs) and two transmembrane domains (Fig. 11-41). In some cases, all these domains are in a single long polypeptide other ABC transporters have two subunits, each contributing an NBD and a domain with six (or in some cases ten) transmembrane helices. Although many of the ABC transporters are in the plasma membrane, some types are also found in the endoplasmic reticulum and in the membranes of mitochondria and lysosomes. Most ABC transporters act as pumps, but at least some members of the superfamily act as ion channels that are opened and closed by ATP hydrolysis. The CFTR transporter (Box 11-3) is a Cl- channel operated by ATP hydrolysis. 

Yang R, Cui L, Hou Y, et al. ATP binding to the first nucleotide binding domain of multidrug resistance-associated protein plays a regulatory role at low nucleotide concentration, whereas ATP hydrolysis at the second plays a dominant role in ATP-dependent leukotriene C4 transport. J Biol Chem 2003 278 30764—30771. 

Szabo K, Welker E, Bakos E, Muller M, Roninson I, Varadi A, Sarkadi B (1998) Drug-stimulated nucleotide trapping in the human multidrug transporter MDR1. Cooperation of the nucleotide binding domains. J Biol Chem 273 10132-10138... 

Jha. S., Kamani. N.. Dhar, S.K., Mukhopadhayay. K.. Shukla, S., Saini, P., Mukhopadhayay. G.. and Prasad, R. (2003) Purification and characterization of the N-terminal nucleotide binding domain of an ABC drug transporter of Candida albicans uncommon cysteine 193 of Walker A is critical for ATP hydrolysis. Biochemistry, 42 (36), 10822-10832. 

Proff, C. and Kolling, R. (2001) Functional asymmetry of the two nucleotide binding domains in the ABC transporter Ste6. Molecular ej General Genetics, 264 (6). 883-893. 

All ABC transporters contain four essential modules, two nucleotide binding domains (N BDs) and two transmembrane domains (TMDs). These four modules can be encoded by four separate genes or fused pairwise in all possible combinations [35, 37]. Bacterial MDRs are usually homo- or heterodimers in which one NBD is fused to one TMD. This is the case for the most well-studied bacterial ABC MDRs, LmrA [38] and LmrCD [39], both from Lactococcus lactis. 

Moody, J.E. and Thomas, P.J. (2005) Nucleotide binding domain interactions during the mechanochemical reaction cycle of ATP-binding cassette transporters. Journal of Bioenergetics and Biomembranes, Bl (6), 475-479. 

Rai, V., Shukla, S., Jha, S., Komath, S.S., and Prasad, R. (2005) Functional characterization of N-terminal nucleotide binding domain (NBD-1) of a major ABC drug transporter Cdrlp of Candida albicans uncommon but conserved Trp326 of Walker B is important for ATP binding. Biochemistry, 44, 6650-6661. 

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