“Pyruvate Carboxylase, Structure and Function”

Part of the Subcellular Biochemistry book series (SCBI, volume 83)


Pyruvate carboxylase is a metabolic enzyme that fuels the tricarboxylic acid cycle with one of its intermediates and also participates in the first step of gluconeogenesis. This large enzyme is multifunctional, and each subunit contains two active sites that catalyze two consecutive reactions that lead to the carboxylation of pyruvate into oxaloacetate, and a binding site for acetyl-CoA, an allosteric regulator of the enzyme. Pyruvate carboxylase oligomers arrange in tetramers and covalently attached biotins mediate the transfer of carboxyl groups between distant active sites. In this chapter, some of the recent findings on pyruvate carboxylase functioning are presented, with special focus on the structural studies of the full length enzyme. The emerging picture reveals large movements of domains that even change the overall quaternary organization of pyruvate carboxylase tetramers during catalysis.


Multifunctional enzyme Biotin-dependent carboxylase Pyruvate carboxylase Allosteric regulation Acetyl-CoA 


  1. Adina-Zada A, Jitrapakdee S, Surinya KH, McIldowie MJ, Piggott MJ, Cleland WW, Wallace JC, Attwood PV (2008) Insights into the mechanism and regulation of pyruvate carboxylase by characterisation of a biotin-deficient mutant of the Bacillus thermodenitrificans enzyme. Int J Biochem Cell Biol 40(9):1743–1752. doi:10.1016/j.biocel.2008.01.001 CrossRefPubMedGoogle Scholar
  2. Adina-Zada A, Sereeruk C, Jitrapakdee S, Zeczycki TN, St Maurice M, Cleland WW, Wallace JC, Attwood PV (2012a) Roles of Arg427 and Arg472 in the binding and allosteric effects of acetyl CoA in pyruvate carboxylase. Biochemistry 51(41):8208–8217CrossRefPubMedPubMedCentralGoogle Scholar
  3. Adina-Zada A, Zeczycki TN, Attwood PV (2012b) Regulation of the structure and activity of pyruvate carboxylase by acetyl CoA. Arch Biochem Biophys 519(2):118–130. doi:10.1016/j.abb.2011.11.015 CrossRefPubMedGoogle Scholar
  4. Adina-Zada A, Zeczycki TN, St Maurice M, Jitrapakdee S, Cleland WW, Attwood PV (2012c) Allosteric regulation of the biotin-dependent enzyme pyruvate carboxylase by acetyl-CoA. Biochem Soc Trans 40(3):567–572. doi:10.1042/BST20120041 CrossRefPubMedGoogle Scholar
  5. Ashman LK, Keech DB (1975) Sheep kidney pyruvate carboxylase. Studies on the coupling of adenosine triphosphate hydrolysis and CO2 fixation. J Biol Chem 250(1):14–21PubMedGoogle Scholar
  6. Attwood PV, Graneri BD (1992) Bicarbonate-dependent ATP cleavage catalysed by pyruvate carboxylase in the absence of pyruvate. Biochem J 287(Pt 3):1011–1017CrossRefPubMedPubMedCentralGoogle Scholar
  7. Attwood PV, Wallace JC (2002) Chemical and catalytic mechanisms of carboxyl transfer reactions in biotin-dependent enzymes. Acc Chem Res 35(2):113–120CrossRefPubMedGoogle Scholar
  8. Bizeau ME, Short C, Thresher JS, Commerford SR, Willis WT, Pagliassotti MJ (2001) Increased pyruvate flux capacities account for diet-induced increases in gluconeogenesis in vitro. Am J Phys Regul Integr Comp Phys 281(2):R427–R433Google Scholar
  9. Cao Z, Zhou Y, Zhu S, Feng J, Chen X, Liu S, Peng N, Yang X, Xu G, Zhu Y (2016) Pyruvate Carboxylase Activates the RIG-I-like Receptor-Mediated Antiviral Immune Response by Targeting the MAVS signalosome. Sci Report 6:22002. doi:10.1038/srep22002 CrossRefGoogle Scholar
  10. Carbone MA, MacKay N, Ling M, Cole DE, Douglas C, Rigat B, Feigenbaum A, Clarke JT, Haworth JC, Greenberg CR, Seargeant L, Robinson BH (1998) Amerindian pyruvate carboxylase deficiency is associated with two distinct missense mutations. Am J Hum Genet 62(6):1312–1319CrossRefPubMedPubMedCentralGoogle Scholar
  11. Cardaci S, Zheng L, MacKay G, van den Broek NJ, MacKenzie ED, Nixon C, Stevenson D, Tumanov S, Bulusu V, Kamphorst JJ, Vazquez A, Fleming S, Schiavi F, Kalna G, Blyth K, Strathdee D, Gottlieb E (2015) Pyruvate carboxylation enables growth of SDH-deficient cells by supporting aspartate biosynthesis. Nat Cell Biol 17(10):1317–1326. doi:10.1038/ncb3233 CrossRefPubMedPubMedCentralGoogle Scholar
  12. Chou CY, Yu LP, Tong L (2009) Crystal structure of biotin carboxylase in complex with substrates and implications for its catalytic mechanism. J Biol Chem 284(17):11690–11697. doi:10.1074/jbc.M805783200 CrossRefPubMedPubMedCentralGoogle Scholar
  13. de Queiroz MS, Waldrop GL (2007) Modeling and numerical simulation of biotin carboxylase kinetics: implications for half-sites reactivity. J Theor Biol 246(1):167–175CrossRefPubMedGoogle Scholar
  14. DeVivo DC, Haymond MW, Leckie MP, Bussman YL, McDougal DB Jr, Pagliara AS (1977) The clinical and biochemical implications of pyruvate carboxylase deficiency. J Clin Endocrinol Metab 45(6):1281–1296. doi:10.1210/jcem-45-6-1281 CrossRefPubMedGoogle Scholar
  15. Duangpan S, Jitrapakdee S, Adina-Zada A, Byrne L, Zeczycki TN, St Maurice M, Cleland WW, Wallace JC, Attwood PV (2010) Probing the catalytic roles of Arg548 and Gln552 in the carboxyl transferase domain of the Rhizobium etli pyruvate carboxylase by site-directed mutagenesis. Biochemistry 49(15):3296–3304CrossRefPubMedPubMedCentralGoogle Scholar
  16. Dugal BS (1973) Apparent co-operative effect of acetyl-CoA on pigeon liver pyruvate carboxylase. FEBS Lett 30(2):181–184CrossRefPubMedGoogle Scholar
  17. Easterbrook-Smith SB, Wallace JC, Keech DB (1978) A reappraisal of the reaction pathway of pyruvate carboxylase. Biochem J 169(1):225–228CrossRefPubMedPubMedCentralGoogle Scholar
  18. Easterbrook-Smith SB, Campbell AJ, Keech DB, Wallace JC (1979) The atypical velocity response by pyruvate carboxylase to increasing concentrations of acetyl-coenzyme A. Biochem J 179(3):497–502CrossRefPubMedPubMedCentralGoogle Scholar
  19. Fan C, Chou CY, Tong L, Xiang S (2012) Crystal structure of urea carboxylase provides insights into the carboxyltransfer reaction. J Biol Chem 287(12):9389–9398. doi:10.1074/jbc.M111.319475 CrossRefPubMedPubMedCentralGoogle Scholar
  20. Fawaz MV, Topper ME, Firestine SM (2011) The ATP-grasp enzymes. Bioorg Chem 39(5–6):185–191. doi:10.1016/j.bioorg.2011.08.004 CrossRefPubMedPubMedCentralGoogle Scholar
  21. Freedman AD, Kohn L (1964) Pyruvate metabolism and control: factors affecting pyruvic carboxylase activity. Science (New York, NY) 145(3627):58–60CrossRefGoogle Scholar
  22. Galperin MY, Koonin EV (1997) A diverse superfamily of enzymes with ATP-dependent carboxylate-amine/thiol ligase activity. Protein Sci 6(12):2639–2643. doi:10.1002/pro.5560061218 CrossRefPubMedPubMedCentralGoogle Scholar
  23. Gamberino WC, Berkich DA, Lynch CJ, Xu B, LaNoue KF (1997) Role of pyruvate carboxylase in facilitation of synthesis of glutamate and glutamine in cultured astrocytes. J Neurochem 69(6):2312–2325CrossRefPubMedGoogle Scholar
  24. Garcia-Cazorla A, Rabier D, Touati G, Chadefaux-Vekemans B, Marsac C, de Lonlay P, Saudubray JM (2006) Pyruvate carboxylase deficiency: metabolic characteristics and new neurological aspects. Ann Neurol 59(1):121–127. doi:10.1002/ana.20709 CrossRefPubMedGoogle Scholar
  25. Goodall GJ, Baldwin GS, Wallace JC, Keech DB (1981) Factors that influence the translocation of the N-carboxybiotin moiety between the two sub-sites of pyruvate carboxylase. Biochem J 199(3):603–609CrossRefPubMedPubMedCentralGoogle Scholar
  26. Goss JA, Cohen ND, Utter MF (1981) Characterization of the subunit structure of pyruvate carboxylase from Pseudomonas citronellolis. J Biol Chem 256(22):11819–11825PubMedGoogle Scholar
  27. Gray LR, Tompkins SC, Taylor EB (2014) Regulation of pyruvate metabolism and human disease. Cell Mol Life Sci 71(14):2577–2604. doi:10.1007/s00018-013-1539-2 CrossRefPubMedGoogle Scholar
  28. Huang CS, Sadre-Bazzaz K, Shen Y, Deng B, Zhou ZH, Tong L (2010) Crystal structure of the alpha(6)beta(6) holoenzyme of propionyl-coenzyme A carboxylase. Nature 466(7309):1001–1005. doi:10.1038/nature09302 CrossRefPubMedPubMedCentralGoogle Scholar
  29. Huang CS, Ge P, Zhou ZH, Tong L (2012) An unanticipated architecture of the 750-kDa alpha6beta6 holoenzyme of 3-methylcrotonyl-CoA carboxylase. Nature 481(7380):219–223. doi:10.1038/nature10691 CrossRefGoogle Scholar
  30. Janiyani K, Bordelon T, Waldrop GL, Cronan JE Jr (2001) Function of Escherichia coli biotin carboxylase requires catalytic activity of both subunits of the homodimer. J Biol Chem 276(32):29864–29870. doi:10.1074/jbc.M104102200 CrossRefPubMedGoogle Scholar
  31. Jitrapakdee S, St Maurice M, Rayment I, Cleland WW, Wallace JC, Attwood PV (2008) Structure, mechanism and regulation of pyruvate carboxylase. Biochem J 413(3):369–387CrossRefPubMedPubMedCentralGoogle Scholar
  32. Jurado AR, Huang CS, Zhang X, Zhou ZH, Tong L (2015) Structure and substrate selectivity of the 750-kDa alpha6beta6 holoenzyme of geranyl-CoA carboxylase. Nat Commun 6:8986. doi:10.1038/ncomms9986 CrossRefPubMedPubMedCentralGoogle Scholar
  33. Kaziro Y, Hass LF, Boyer PD, Ochoa S (1962) Mechanism of the propionyl carboxylase reaction. II. Isotopic exchange and tracer experiments. J Biol Chem 237:1460–1468PubMedGoogle Scholar
  34. Keech B, Barritt GJ (1967) Allosteric activation of sheep kidney pyruvate carboxylase by the magnesium ion (Mg2+) and the magnesium adenosine triphosphate ion (MgATP2-). J Biol Chem 242(9):1983–1987PubMedGoogle Scholar
  35. Knowles JR (1989) The mechanism of biotin-dependent enzymes. Annu Rev Biochem 58:195–221CrossRefPubMedGoogle Scholar
  36. Kondo S, Nakajima Y, Sugio S, Yong-Biao J, Sueda S, Kondo H (2004) Structure of the biotin carboxylase subunit of pyruvate carboxylase from Aquifex aeolicus at 2.2 A resolution. Acta Crystallogr D Biol Crystallogr 60(Pt 3):486–492. doi:10.1107/S0907444904000423 CrossRefPubMedGoogle Scholar
  37. Kondo S, Nakajima Y, Sugio S, Sueda S, Islam MN, Kondo H (2007) Structure of the biotin carboxylase domain of pyruvate carboxylase from Bacillus thermodenitrificans. Acta Crystallogr D Biol Crystallogr 63(Pt 8):885–890. doi:10.1107/S0907444907029423 CrossRefPubMedGoogle Scholar
  38. Lai H, Kraszewski JL, Purwantini E, Mukhopadhyay B (2006) Identification of pyruvate carboxylase genes in Pseudomonas aeruginosa PAO1 and development of a P. aeruginosa-based overexpression system for alpha4- and alpha4beta4-type pyruvate carboxylases. Appl Environ Microbiol 72(12):7785–7792. doi:10.1128/AEM.01564-06 CrossRefPubMedPubMedCentralGoogle Scholar
  39. Lasso G, Yu LP, Gil D, Xiang S, Tong L, Valle M (2010) Cryo-EM analysis reveals new insights into the mechanism of action of pyruvate carboxylase. Structure 18(10):1300–1310CrossRefPubMedPubMedCentralGoogle Scholar
  40. Lasso G, Yu LP, Gil D, Lazaro M, Tong L, Valle M (2014) Functional conformations for pyruvate carboxylase during catalysis explored by cryoelectron microscopy. Structure 22(6):911–922. doi:10.1016/j.str.2014.04.011 CrossRefPubMedPubMedCentralGoogle Scholar
  41. Legge GB, Branson JP, Attwood PV (1996) Effects of acetyl CoA on the pre-steady-state kinetics of the biotin carboxylation reaction of pyruvate carboxylase. Biochemistry 35(12):3849–3856. doi:10.1021/bi952797q CrossRefPubMedGoogle Scholar
  42. Lietzan AD, Menefee AL, Zeczycki TN, Kumar S, Attwood PV, Wallace JC, Cleland WW, St Maurice M (2011) Interaction between the biotin carboxyl carrier domain and the biotin carboxylase domain in pyruvate carboxylase from Rhizobium etli. Biochemistry 50(45):9708–9723CrossRefPubMedPubMedCentralGoogle Scholar
  43. Lietzan AD, St Maurice M (2013a) Insights into the carboxyltransferase reaction of pyruvate carboxylase from the structures of bound product and intermediate analogs. Biochem Biophys Res Commun 441(2):377–382. doi:10.1016/j.bbrc.2013.10.066 CrossRefPubMedPubMedCentralGoogle Scholar
  44. Lietzan AD, St Maurice M (2013b) A substrate-induced biotin binding pocket in the carboxyl transferase domain of pyruvate carboxylase. J Biol Chem 288(27):19915–19925Google Scholar
  45. Lietzan AD, Lin Y, St Maurice M (2014) The role of biotin and oxamate in the carboxyltransferase reaction of pyruvate carboxylase. Arch Biochem Biophys 562:70–79. doi:10.1016/j.abb.2014.08.008 CrossRefPubMedPubMedCentralGoogle Scholar
  46. Lu D, Mulder H, Zhao P, Burgess SC, Jensen MV, Kamzolova S, Newgard CB, Sherry AD (2002) 13C NMR isotopomer analysis reveals a connection between pyruvate cycling and glucose-stimulated insulin secretion (GSIS). Proc Natl Acad Sci U S A 99(5):2708–2713. doi:10.1073/pnas.052005699 CrossRefPubMedPubMedCentralGoogle Scholar
  47. Marin-Valencia I, Roe CR, Pascual JM (2010) Pyruvate carboxylase deficiency: mechanisms, mimics and anaplerosis. Mol Genet Metab 101(1):9–17CrossRefPubMedGoogle Scholar
  48. Menefee AL, Zeczycki TN (2014) Nearly 50 years in the making: defining the catalytic mechanism of the multifunctional enzyme, pyruvate carboxylase. FEBS J 281(5):1333–1354. doi:10.1111/febs.12713 CrossRefPubMedGoogle Scholar
  49. Mochalkin I, Miller JR, Evdokimov A, Lightle S, Yan C, Stover CK, Waldrop GL (2008) Structural evidence for substrate-induced synergism and half-sites reactivity in biotin carboxylase. Protein Sci 17(10):1706–1718CrossRefPubMedPubMedCentralGoogle Scholar
  50. Monnot S, Serre V, Chadefaux-Vekemans B, Aupetit J, Romano S, De Lonlay P, Rival JM, Munnich A, Steffann J, Bonnefont JP (2009) Structural insights on pathogenic effects of novel mutations causing pyruvate carboxylase deficiency. Hum Mutat 30(5):734–740. doi:10.1002/humu.20908 CrossRefPubMedGoogle Scholar
  51. Mukhopadhyay B, Stoddard SF, Wolfe RS (1998) Purification, regulation, and molecular and biochemical characterization of pyruvate carboxylase from Methanobacterium thermoautotrophicum strain deltaH. J Biol Chem 273(9):5155–5166CrossRefPubMedGoogle Scholar
  52. Mukhopadhyay B, Patel VJ, Wolfe RS (2000) A stable archaeal pyruvate carboxylase from the hyperthermophile Methanococcus jannaschii. Arch Microbiol 174(6):406–414CrossRefPubMedGoogle Scholar
  53. Mukhopadhyay B, Purwantini E, Kreder CL, Wolfe RS (2001) Oxaloacetate synthesis in the methanarchaeon Methanosarcina barkeri: pyruvate carboxylase genes and a putative Escherichia coli-type bifunctional biotin protein ligase gene (bpl/birA) exhibit a unique organization. J Bacteriol 183(12):3804–3810. doi:10.1128/JB.183.12.3804-3810.2001 CrossRefPubMedPubMedCentralGoogle Scholar
  54. Ogita T, Knowles JR (1988) On the intermediacy of carboxyphosphate in biotin-dependent carboxylations. Biochemistry 27(21):8028–8033CrossRefPubMedGoogle Scholar
  55. Ostergaard E, Duno M, Moller LB, Kalkanoglu-Sivri HS, Dursun A, Aliefendioglu D, Leth H, Dahl M, Christensen E, Wibrand F (2013) Novel Mutations in the PC Gene in Patients with Type B Pyruvate Carboxylase Deficiency. JIMD Rep 9:1–5. doi:10.1007/8904_2012_173 CrossRefPubMedGoogle Scholar
  56. Phannasil P, Thuwajit C, Warnnissorn M, Wallace JC, MacDonald MJ, Jitrapakdee S (2015) Pyruvate carboxylase is up-regulated in breast cancer and essential to support growth and invasion of MDA-MB-231 cells. PLoS One 10(6):e0129848. doi:10.1371/journal.pone.0129848 CrossRefPubMedPubMedCentralGoogle Scholar
  57. Robinson BH (2006) Lactic acidemia and mitochondrial disease. Mol Genet Metab 89(1–2):3–13. doi:10.1016/j.ymgme.2006.05.015 CrossRefPubMedGoogle Scholar
  58. Salto R, Sola M, Oliver FJ, Vargas AM (1996) Effects of starvation, diabetes and carbon tetrachloride intoxication on rat kidney cortex and liver pyruvate carboxylase levels. Arch Physiol Biochem 104(7):845–850. doi:10.1076/apab.104.7.845.13111 CrossRefPubMedGoogle Scholar
  59. Saudubray JM, Marsac C, Cathelineau CL, Besson Leaud M, Leroux JP (1976) Neonatal congenital lactic acidosis with pyruvate carboxylase deficiency in two siblings. Acta Paediatr Scand 65(6):717–724CrossRefPubMedGoogle Scholar
  60. Scheres SH (2010) Classification of structural heterogeneity by maximum-likelihood methods. Methods Enzymol 482:295–320CrossRefPubMedPubMedCentralGoogle Scholar
  61. Scheres SH (2012) RELION: implementation of a Bayesian approach to cryo-EM structure determination. J Struct Biol 180(3):519–530CrossRefPubMedPubMedCentralGoogle Scholar
  62. Scrutton MC, Utter MF (1967) Pyruvate carboxylase IX. Some properties of the activation by certain acyl derivatives of coenzyme A. J Biol Chem 242(8):1723–1735PubMedGoogle Scholar
  63. Scrutton MC, Keech DB, Utter MF (1965) Pyruvate carboxylase. IV. Partial reactions and the locus of activation by acetyl coenzyme A. J Biol Chem 240:574–581PubMedGoogle Scholar
  64. Sellers K, Fox MP, Bousamra M 2nd, Slone SP, Higashi RM, Miller DM, Wang Y, Yan J, Yuneva MO, Deshpande R, Lane AN, Fan TW (2015) Pyruvate carboxylase is critical for non-small-cell lung cancer proliferation. J Clin Invest 125(2):687–698. doi:10.1172/JCI72873 CrossRefPubMedPubMedCentralGoogle Scholar
  65. Shen Y, Chou CY, Chang GG, Tong L (2006) Is dimerization required for the catalytic activity of bacterial biotin carboxylase? Mol Cell 22(6):807–818CrossRefPubMedGoogle Scholar
  66. St Maurice M, Reinhardt L, Surinya KH, Attwood PV, Wallace JC, Cleland WW, Rayment I (2007) Domain architecture of pyruvate carboxylase, a biotin-dependent multifunctional enzyme. Science (New York, NY) 317(5841):1076–1079CrossRefGoogle Scholar
  67. Sureka K, Choi PH, Precit M, Delince M, Pensinger DA, Huynh TN, Jurado AR, Goo YA, Sadilek M, Iavarone AT, Sauer JD, Tong L, Woodward JJ (2014) The cyclic dinucleotide c-di-AMP is an allosteric regulator of metabolic enzyme function. Cell 158(6):1389–1401. doi:10.1016/j.cell.2014.07.046 CrossRefPubMedPubMedCentralGoogle Scholar
  68. Thoden JB, Blanchard CZ, Holden HM, Waldrop GL (2000) Movement of the biotin carboxylase B-domain as a result of ATP binding. J Biol Chem 275(21):16183–16190CrossRefPubMedGoogle Scholar
  69. Tipton PA, Cleland WW (1988) Catalytic mechanism of biotin carboxylase: steady-state kinetic investigations. Biochemistry 27(12):4317–4325CrossRefPubMedGoogle Scholar
  70. Tong L (2013) Structure and function of biotin-dependent carboxylases. Cell Mol Life Sci 70(5):863–891CrossRefPubMedGoogle Scholar
  71. Tran TH, Hsiao YS, Jo J, Chou CY, Dietrich LE, Walz T, Tong L (2015) Structure and function of a single-chain, multi-domain long-chain acyl-CoA carboxylase. Nature 518(7537):120–124. doi:10.1038/nature13912 CrossRefPubMedGoogle Scholar
  72. Utter MF, Keech DB (1960) Formation of oxaloacetate from pyruvate and carbon dioxide. J Biol Chem 235:PC17–PC18PubMedGoogle Scholar
  73. Waldrop GL, Rayment I, Holden HM (1994) Three-dimensional structure of the biotin carboxylase subunit of acetyl-CoA carboxylase. Biochemistry 33(34):10249–10256CrossRefPubMedGoogle Scholar
  74. Waldrop GL, Holden HM, St Maurice M (2013) The enzymes of biotin dependent CO(2) metabolism: what structures reveal about their reaction mechanisms. Protein Sci 21(11):1597–1619CrossRefGoogle Scholar
  75. Wang D, De Vivo D (1993) Pyruvate Carboxylase Deficiency. In: Pagon RA, Adam MP, Ardinger HH et al. (eds) GeneReviews(R). Seattle (WA)Google Scholar
  76. Warburg O (1956) On the origin of cancer cells. Science (New York, NY) 123(3191):309–314CrossRefGoogle Scholar
  77. Warren GB, Tipton KF (1974) The role of acetyl-CoA in the reaction pathway of pig-liver pyruvate carboxylase. Eur J Biochem 47(3):549–554CrossRefPubMedGoogle Scholar
  78. Wei J, Tong L (2015) Crystal structure of the 500-kDa yeast acetyl-CoA carboxylase holoenzyme dimer. Nature 526(7575):723–727. doi:10.1038/nature15375 CrossRefPubMedPubMedCentralGoogle Scholar
  79. Wexler ID, Kerr DS, Du Y, Kaung MM, Stephenson W, Lusk MM, Wappner RS, Higgins JJ (1998) Molecular characterization of pyruvate carboxylase deficiency in two consanguineous families. Pediatr Res 43(5):579–584. doi:10.1203/00006450-199805000-00004 CrossRefPubMedGoogle Scholar
  80. Xiang S, Tong L (2008) Crystal structures of human and Staphylococcus aureus pyruvate carboxylase and molecular insights into the carboxyltransfer reaction. Nat Struct Mol Biol 15(3):295–302CrossRefPubMedGoogle Scholar
  81. Yu LP, Xiang S, Lasso G, Gil D, Valle M, Tong L (2009) A symmetrical tetramer for S. Aureus pyruvate carboxylase in complex with coenzyme A. Structure 17(6):823–832CrossRefPubMedPubMedCentralGoogle Scholar
  82. Yu LP, Chou CY, Choi PH, Tong L (2013) Characterizing the importance of the biotin carboxylase domain dimer for Staphylococcus aureus pyruvate carboxylase catalysis. Biochemistry 52(3):488–496CrossRefPubMedPubMedCentralGoogle Scholar
  83. Zeczycki TN, St Maurice M, Jitrapakdee S, Wallace JC, Attwood PV, Cleland WW (2009) Insight into the carboxyl transferase domain mechanism of pyruvate carboxylase from Rhizobium etli. Biochemistry 48(20):4305–4313CrossRefPubMedPubMedCentralGoogle Scholar
  84. Zeczycki TN, Maurice MS, Attwood PV (2010) Inhibitors of Pyruvate Carboxylase. Open Enzym Inhib J 3:8–26. doi:10.2174/1874940201003010008 CrossRefPubMedPubMedCentralGoogle Scholar
  85. Zeczycki TN, Menefee AL, Adina-Zada A, Jitrapakdee S, Surinya KH, Wallace JC, Attwood PV, St Maurice M, Cleland WW (2011a) Novel insights into the biotin carboxylase domain reactions of pyruvate carboxylase from Rhizobium etli. Biochemistry 50(45):9724–9737CrossRefPubMedPubMedCentralGoogle Scholar
  86. Zeczycki TN, Menefee AL, Jitrapakdee S, Wallace JC, Attwood PV, St Maurice M, Cleland WW (2011b) Activation and inhibition of pyruvate carboxylase from Rhizobium etli. Biochemistry 50(45):9694–9707CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2017

Authors and Affiliations

  1. 1.Structural Biology UnitCenter for Cooperative Research in Biosciences, CIC bioGUNEDerioSpain

Personalised recommendations