Sodium-transporting carboxylic acid decarboxylase
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.[1]
Function
[edit]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.[2] These systems have been characterized only from bacteria.
The generalized reaction for the NaT-DC family is:
R - CO−
2 (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
[edit]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+.[3]
Structure
[edit]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 (3GF3).[4] 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.[4][5]
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).[1][4]
See also
[edit]References
[edit]- ^ a b "3.B.1 The Na+-transporting Carboxylic Acid Decarboxylase (NaT-DC) Family". TCDB. Retrieved 7 April 2016.
- ^ Boiangiu CD, Jayamani E, Brügel D, Herrmann G, Kim J, Forzi L, Hedderich R, Vgenopoulou I, Pierik AJ, Steuber J, Buckel W (1 January 2005). "Sodium ion pumps and hydrogen production in glutamate fermenting anaerobic bacteria". Journal of Molecular Microbiology and Biotechnology. 10 (2–4): 105–19. doi:10.1159/000091558. PMID 16645308. S2CID 22898166.
- ^ Granjon T, Maniti O, Auchli Y, Dahinden P, Buchet R, Marcillat O, Dimroth P (June 2010). "Structure-function relations in oxaloacetate decarboxylase complex. Fluorescence and infrared approaches to monitor oxomalonate and Na(+) binding effect". PLOS ONE. 5 (6): e10935. Bibcode:2010PLoSO...510935G. doi:10.1371/journal.pone.0010935. PMC 2881705. PMID 20543879.
- ^ a b c Wendt KS, Schall I, Huber R, Buckel W, Jacob U (July 2003). "Crystal structure of the carboxyltransferase subunit of the bacterial sodium ion pump glutaconyl-coenzyme A decarboxylase". The EMBO Journal. 22 (14): 3493–502. doi:10.1093/emboj/cdg358. PMC 165628. PMID 12853465.
- ^ Braune A, Bendrat K, Rospert S, Buckel W (January 1999). "The sodium ion translocating glutaconyl-CoA decarboxylase from Acidaminococcus fermentans: cloning and function of the genes forming a second operon". Molecular Microbiology. 31 (2): 473–87. doi:10.1046/j.1365-2958.1999.01189.x. PMID 10027965. S2CID 35018668.
Further reading
[edit]- Balsera M, Buey RM, Li XD (March 2011). "Quaternary structure of the oxaloacetate decarboxylase membrane complex and mechanistic relationships to pyruvate carboxylases". The Journal of Biological Chemistry. 286 (11): 9457–67. doi:10.1074/jbc.M110.197442. PMC 3058996. PMID 21209096.
- Buckel W (May 2001). "Sodium ion-translocating decarboxylases". Biochimica et Biophysica Acta (BBA) - Bioenergetics. 1505 (1): 15–27. doi:10.1016/s0005-2728(00)00273-5. PMID 11248185.
- Cohen GN, Barbe V, Flament D, Galperin M, Heilig R, Lecompte O, Poch O, Prieur D, Quérellou J, Ripp R, Thierry JC, Van der Oost J, Weissenbach J, Zivanovic Y, Forterre P (March 2003). "An integrated analysis of the genome of the hyperthermophilic archaeon Pyrococcus abyssi". Molecular Microbiology. 47 (6): 1495–512. doi:10.1046/j.1365-2958.2003.03381.x. PMID 12622808. S2CID 28940586.
- Dimroth P (January 1997). "Primary sodium ion translocating enzymes". Biochimica et Biophysica Acta (BBA) - Bioenergetics. 1318 (1–2): 11–51. doi:10.1016/s0005-2728(96)00127-2. PMID 9030254.
- Dimroth P, Schink B (August 1998). "Energy conservation in the decarboxylation of dicarboxylic acids by fermenting bacteria" (PDF). Archives of Microbiology. 170 (2): 69–77. Bibcode:1998ArMic.170...69D. doi:10.1007/s002030050616. PMID 9683642. S2CID 553431.
- Dimroth P, Jockel P, Schmid M (May 2001). "Coupling mechanism of the oxaloacetate decarboxylase Na(+) pump". Biochimica et Biophysica Acta (BBA) - Bioenergetics. 1505 (1): 1–14. doi:10.1016/s0005-2728(00)00272-3. PMID 11248184.
- Huder JB, Dimroth P (November 1993). "Sequence of the sodium ion pump methylmalonyl-CoA decarboxylase from Veillonella parvula". The Journal of Biological Chemistry. 268 (33): 24564–71. doi:10.1016/S0021-9258(19)74504-9. PMID 8227015.
- Schaffitzel C, Berg M, Dimroth P, Pos KM (May 1998). "Identification of an Na+-dependent malonate transporter of Malonomonas rubra and its dependence on two separate genes". Journal of Bacteriology. 180 (10): 2689–93. doi:10.1128/JB.180.10.2689-2693.1998. PMC 107221. PMID 9573154.
- Woehlke G, Wifling K, Dimroth P (November 1992). "Sequence of the sodium ion pump oxaloacetate decarboxylase from Salmonella typhimurium". The Journal of Biological Chemistry. 267 (32): 22798–803. doi:10.1016/S0021-9258(18)50017-X. PMID 1331067.
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