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
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
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]
Crystal 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 (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
Further reading
- Balsera, Monica; Buey, Ruben M.; Li, Xiao-Dan (2011-03-18). "Quaternary structure of the oxaloacetate decarboxylase membrane complex and mechanistic relationships to pyruvate carboxylases". The Journal of Biological Chemistry 286 (11): 9457–9467.doi:10.1074/jbc.M110.197442. ISSN 1083-351X.PMC 3058996. PMID 21209096.
- Berg, M.; Hilbi, H.; Dimroth, P. (1997-04-01)."Sequence of a gene cluster from Malonomonas rubra encoding components of the malonate decarboxylase Na+ pump and evidence for their function". European journal of biochemistry / FEBS 245 (1): 103–115. ISSN 0014-2956.PMID 9128730.
- Buckel, W. (2001-05-01). "Sodium ion-translocating decarboxylases". Biochimica et Biophysica Acta 1505 (1): 15–27. ISSN 0006-3002. PMID 11248185.
- Cohen, Georges N.; Barbe, Valérie; Flament, Didier; Galperin, Michael; Heilig, Roland; Lecompte, Odile; Poch, Olivier; Prieur, Daniel; Quérellou, Joël (2003-03-01)."An integrated analysis of the genome of the hyperthermophilic archaeon Pyrococcus abyssi". Molecular Microbiology 47 (6): 1495–1512. ISSN 0950-382X.PMID 12622808.
- Dimroth, P. (1997-01-16). "Primary sodium ion translocating enzymes". Biochimica et Biophysica Acta1318 (1-2): 11–51. ISSN 0006-3002. PMID 9030254.
- Dimroth, P.; Schink, B. (1998-08-01). "Energy conservation in the decarboxylation of dicarboxylic acids by fermenting bacteria". Archives of Microbiology 170 (2): 69–77. ISSN 0302-8933. PMID 9683642.
- Dimroth, P.; Jockel, P.; Schmid, M. (2001-05-01). "Coupling mechanism of the oxaloacetate decarboxylase Na(+) pump". Biochimica et Biophysica Acta 1505 (1): 1–14. ISSN 0006-3002. PMID 11248184
- Huder, J. B.; Dimroth, P. (1993-11-25)."Sequence of the sodium ion pump methylmalonyl-CoA decarboxylase from Veillonella parvula". The Journal of Biological Chemistry 268 (33): 24564–24571. ISSN 0021-9258. PMID 8227015.
- Schaffitzel, C.; Berg, M.; Dimroth, P.; Pos, K. M. (1998-05-01). "Identification of an Na+-dependent malonate transporter of Malonomonas rubra and its dependence on two separate genes". Journal of Bacteriology 180 (10): 2689–2693. ISSN 0021-9193.PMC 107221. PMID 9573154.
- Woehlke, G.; Wifling, K.; Dimroth, P. (1992-11-15). "Sequence of the sodium ion pump oxaloacetate decarboxylase from Salmonella typhimurium". The Journal of Biological Chemistry 267 (32): 22798–22803.ISSN 0021-9258. PMID 1331067.
References
- 1 2 "3.B.1 The Na+-transporting Carboxylic Acid Decarboxylase (NaT-DC) Family". TCDB. Retrieved 2016-04-07.
- ↑ Boiangiu, Clara D.; Jayamani, Elamparithi; Brügel, Daniela; Herrmann, Gloria; Kim, Jihoe; Forzi, Lucia; Hedderich, Reiner; Vgenopoulou, Irini; Pierik, Antonio J. (2005-01-01). "Sodium ion pumps and hydrogen production in glutamate fermenting anaerobic bacteria". Journal of Molecular Microbiology and Biotechnology. 10 (2-4): 105–119. doi:10.1159/000091558. ISSN 1464-1801. PMID 16645308.
- ↑ Granjon, Thierry; Maniti, Ofelia; Auchli, Yolanda; Dahinden, Pius; Buchet, René; Marcillat, Olivier; Dimroth, Peter (2010-01-01). "Structure-function relations in oxaloacetate decarboxylase complex. Fluorescence and infrared approaches to monitor oxomalonate and Na(+) binding effect". PloS One. 5 (6): e10935. doi:10.1371/journal.pone.0010935. ISSN 1932-6203. PMC 2881705. PMID 20543879.
- 1 2 3 Wendt, Kerstin S.; Schall, Iris; Huber, Robert; Buckel, Wolfgang; Jacob, Uwe (2003-07-15). "Crystal structure of the carboxyltransferase subunit of the bacterial sodium ion pump glutaconyl-coenzyme A decarboxylase". The EMBO journal. 22 (14): 3493–3502. doi:10.1093/emboj/cdg358. ISSN 0261-4189. PMC 165628. PMID 12853465.
- ↑ Braune, A.; Bendrat, K.; Rospert, S.; Buckel, W. (1999-01-01). "The sodium ion translocating glutaconyl-CoA decarboxylase from Acidaminococcus fermentans: cloning and function of the genes forming a second operon". Molecular Microbiology. 31 (2): 473–487. doi:10.1046/j.1365-2958.1999.01189.x. ISSN 0950-382X. PMID 10027965.
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