PT  - JOURNAL ARTICLE
AU  - Thijs Beuming
AU  - Lei Shi
AU  - Jonathan A. Javitch
AU  - Harel Weinstein
TI  - A Comprehensive Structure-Based Alignment of Prokaryotic and Eukaryotic Neurotransmitter/Na<sup>+</sup> Symporters (NSS) Aids in the Use of the LeuT Structure to Probe NSS Structure and Function
AID  - 10.1124/mol.106.026120
DP  - 2006 Nov 01
TA  - Molecular Pharmacology
PG  - 1630--1642
VI  - 70
IP  - 5
4099  - http://molpharm.aspetjournals.org/content/70/5/1630.short
4100  - http://molpharm.aspetjournals.org/content/70/5/1630.full
SO  - Mol Pharmacol2006 Nov 01; 70
AB  - The recently elucidated crystal structure of a prokaryotic member of the neurotransmitter/sodium symporter (NSS) family (Yamashita et al., 2005) is a major advance toward understanding structure-function relationships in this important class of transporters. To aid in the generalization of these results, we present here a comprehensive sequence alignment of all known prokaryotic and eukaryotic NSS proteins, based on the crystal structure of the leucine transporter from Aquifex aeolicus (LeuT). Regions of low sequence identity between prokaryotic and eukaryotic transporters were aligned with the aid of a number of bioinformatics tools, and the resulting alignments were validated by comparison with experimental data. In a number of regions, including the transmembrane segments 4, 5, and 9 as well as extracellular loops 2, 3, and 4, our alignment differs from the one proposed previously [Nature (Lond)437: 215-223, 2005]. Important similarities and differences among the sequences of NSS proteins in regions likely to determine selectivity in substrate binding and mechanisms of transport regulation are discussed in the context of the LeuT structure and the alignment. The American Society for Pharmacology and Experimental Therapeutics