The Na+-transporting Carboxylic Acid Decarboxylase (NaT-DC) Family (TC# 3.B.1) is a family of porters that belong to the CPA superfamily. Members of this family have been characterized in both Gram-positive and Gram-negative bacteria. A representative list of proteins belonging to the NaT-DC family can be found in the Transporter Classification Database. Function Porters of the NaT-DC family catalyze decarboxylation of a substrate carboxylic acid and use the energy released to drive extrusion of one or two sodium ions (Na+) from the cytoplasm of the cell. These systems have been characterized only from bacteria. The generalized reaction for the NaT-DC family is:R - CO (in) + H+ (out) and 1 or 2 Na+ (in) ←→ R-H + CO2 (in) and 1 or 2 Na+ (out).Distinct enzymes catalyze decarboxylation of (1) oxaloacetate, (2) methylmalonyl-CoA, (3) glutaconyl-CoA and (4) malonate. The oxaloacetate decarboxylases (EC 4.1.1.3; TC# 3.B.1.1.1), methylmalonyl CoA decarboxylases (EC 4.1.1.4; TC# 3.B.1.1.2) and malonate decarboxylases (TC# 3.B.1.1.4) are homologous. Composition Glutaconyl-CoA decarboxylase (EC 4.1.1.70; TC# 3.B.1.1.3) consists of four subunits: α (GcdA, 587 amino acyl residues (aas); catalytic subunit), β (GcdB, 375 aas; 9 TMSs; Na+-transporter subunit), γ (GcdC, 145 aas; biotin-carrier subunit) and δ (GcdD, 107 aas; 1 TMS; the GcdA anchor protein). The catalytic subunit of all four enzyme porters are biotin-containing multi-subunit enzymes. The α-δ subunits of these enzymes are homologous to proteins encoded within the genomes of archaea, such as Pyrococcus abyssi (Cohen et al., 2003). Consequently, NaT-DC family members may be present in archaea as well as bacteria. The α-subunits of the oxaloacetate and methylmalonyl-CoA decarboxylases are homologous to many biotin-containing enzymes including (1) pyruvate carboxylases, (2) homocitrate synthases, (3) biotin carboxyl carrier proteins, (4) isopropylmalate synthases and (5) acyl-CoA carboxylase. The α-subunit of the glutaconate decarboxylase is homologous to propionyl-CoA carboxylase. The crystal structure of the carboxyltransferase at 1.7 Å resolution shows a dimer of TIM barrels with an active site metal ion, identified spectroscopically as Zn2+. Structure The high resolution crystal structure of the α-subunit of the glutaconyl-CoA decarboxylase (Gcdα) of Acidaminococcus fermentans (TC# 3.B.1.1.3) has been solved (). The active site of the dimeric enzyme lies at the interface between the two monomers. The N-terminal domain binds the glutaconyl-CoA, and the C-terminal domain binds the biotinyl lysine moiety. The enzyme transfers CO2 from glutaconyl-CoA to a biotin carrier protein (the γ-subunit) that is subsequently decarboxylated by the carboxybiotin decarboxylation site within the Na+