The Na⁺-transporting Carboxylic Acid Decarboxylase (NaT-DC) Family
TC# 3.B.1
is a family of porters that belong to the

CPA superfamily The cation:proton antiporter (CPA) superfamily is a superfamily of transport proteins named after one of its constituent members, the monovalent cation:proton antiporter-2 (CPA2). CPA1 was considered a member of the superfamily until 2010, when ...

. 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 th
Transporter Classification Database

Function

Porters Porters may refer to: * Porters, Virginia, an unincorporated community in Virginia, United States * Porters, Wisconsin, an unincorporated community in Wisconsin, United States * Porters Ski Area, a ski resort in New Zealand * ''Porters'' (TV series ...

of the NaT-DC family catalyze decarboxylation of a substrate

carboxylic acid In organic chemistry, a carboxylic acid is an organic acid that contains a carboxyl group () attached to an R-group. The general formula of a carboxylic acid is or , with R referring to the alkyl, alkenyl, aryl, or other group. Carboxylic ...

and use the energy released to drive extrusion of one or two sodium ions (Na⁺) from the

cytoplasm In cell biology, the cytoplasm is all of the material within a eukaryotic cell, enclosed by the cell membrane, except for the cell nucleus. The material inside the nucleus and contained within the nuclear membrane is termed the nucleoplasm. The ...

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 Decarboxylation is a chemical reaction that removes a carboxyl group and releases carbon dioxide (CO2). Usually, decarboxylation refers to a reaction of carboxylic acids, removing a carbon atom from a carbon chain. The reverse process, which is t ...

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 Homology may refer to: Sciences Biology *Homology (biology), any characteristic of biological organisms that is derived from a common ancestor *Sequence homology, biological homology between DNA, RNA, or protein sequences * Homologous chrom ...

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 Biotin (or vitamin B7) is one of the B vitamins. It is involved in a wide range of metabolic processes, both in humans and in other organisms, primarily related to the utilization of fats, carbohydrates, and amino acids. The name ''biotin'', bor ...

-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 ''Pyrococcus abyssi'' is a hyperthermophilic archaeon isolated from a deep-sea hydrothermal vent in the North Fiji Basin at . It is anaerobic, sulfur-metabolizing, gram-negative, coccus-shaped and highly motile. Its optimum growth temperature is ...

''
Cohen ''et al''., 2003
. Consequently, NaT-DC family members may be present in

archaea Archaea ( ; singular archaeon ) is a domain of single-celled organisms. These microorganisms lack cell nuclei and are therefore prokaryotes. Archaea were initially classified as bacteria, receiving the name archaebacteria (in the Archaebac ...

as well as

bacteria Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...

. 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 protein Biotin Carboxyl Carrier Protein (BCCP) refers to proteins containing a biotin attachment domain that carry biotin and carboxybiotin throughout the ATP-dependent carboxylation by biotin-dependent carboxylases. In the case of '' E. coli'' Acetyl-C ...

s, (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 barrel The TIM barrel (triose-phosphate isomerase), also known as an alpha/beta barrel, is a conserved protein fold consisting of eight alpha helices (α-helices) and eight parallel beta strands (β-strands) that alternate along the peptide backbone. ...

s 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⁺ pumping beta subunit (Gcdβ). A proposed structure of the holoenzyme positions the water-filled central channel of the Gcdα dimer coaxial with the ion channel in Gcdβ. The central channel is blocked by arginines, which could allow Na⁺ passage by conformational movement or by entry through two side channels. The β-subunits possess 9 transmembrane α-helical spanners (TMSs). The protein may dip into the membrane twice between TMSs III and IV. The most conserved regions are segments IIIa, the first membrane loop following TMS III, and TMS VIII. Conserved residues therein, D203 (IIIa), Y229 (IV) and N373, G377, S382 and R389 (VIII), provide Na⁺ binding sites and the translocation pathway. D203 and S382 may provide two binding sites for the two Na⁺ ions. D203 is absolutely essential for function and may provide the primary intramembranous Na⁺-binding site. The beta subunits of these transporters show sufficient sequence similarity to the Na⁺:H⁺ antiporters of the CPA2 family
TC #2.A.37
to establish homology (K. Studley and M.H. Saier, Jr., unpublished results).

Function

Composition

Structure

See also

References

Further reading