GATMD: -Aminobutyric Acid Transporter Mutagenesis Database

C M Anderson,P D Kidd,S Eskandari

doi:10.1093/database/baq028

Abstract

Since the cloning of the first γ-aminobutyric acid (GABA) transporter (GAT1; SLC6A1) from rat brain in 1990, more than 50 published studies have provided structure–function information on investigator-designed rat and mouse GAT1 mutants. To date, more than 200 of 599 GAT1 residues have been subjected to mutagenesis experiments by substitution with different amino acids, and the resulting transporter functional properties have significantly advanced our understanding of the mechanism of Na+- and Cl–-coupled GABA transport by this important member of the neurotransmitter:sodium symporter family. Moreover, many studies have addressed the functional consequences of amino acid deletion or insertion at various positions along the primary sequence. The enormity of this growing body of structure–function information has prompted us to develop GABA Transporter Mutagenesis Database (GATMD), a web-accessible, relational database of manually annotated biochemical, functional and pharmacological data reported on GAT1—the most intensely studied GABA transporter isoform. As of the last update of GATMD, 52 GAT1 mutagenesis papers have yielded 3360 experimental records, which collectively contain a total of ∼100 000 annotated parameters.Database URL: http://physiology.sci.csupomona.edu/GATMD/

Highlights

In recent years, the proliferation of structure–function studies of proteins via investigator-designed site-directed mutagenesis has led to significant strides in our understanding of molecular, biochemical, cell biological, physiological and pharmacological principles that underlie life processes
The g-aminobutyric acid (GABA) transporters belong to the large neurotransmitter/Na+ symporter family (NSS; 2.A.22 according to the transporter classification system; SLC6 according to the Human Genome Organization classification) [2, 9,10,11,12]
The data included in GABA Transporter Mutagenesis Database (GATMD) are organized around individual ‘experimental records’, which correspond to physical experiments performed on wildtype (WT) and laboratory-designed GABA transporter isoform 1 (GAT1) mutants in order to elucidate one or more aspects of transporter structural, biochemical, functional and/or pharmacological properties

Summary

Introduction

The proliferation of structure–function studies of proteins via investigator-designed site-directed mutagenesis has led to significant strides in our understanding of molecular, biochemical, cell biological, physiological and pharmacological principles that underlie life processes. The GABA transporters belong to the large neurotransmitter/Na+ symporter family (NSS; 2.A.22 according to the transporter classification system; SLC6 according to the Human Genome Organization classification) [2, 9,10,11,12]. Solute transport in these transporters is driven by the electrochemical potential gradient of Na+ and Cl– and, 2 Na+ ions and 1 Cl– ion are cotranslocated with GABA during each transport cycle [13,14,15,16,17,18,19]. We report the development and web implementation of GABA Transporter Mutagenesis Database (GATMD), a comprehensive, web-accessible, relational database for managing published GAT1 mutagenesis data. GATMD is available on the Internet at http://physiology.sci.csupomona.edu/GATMD/

Methods

Findings

Discussion