3bg9 Citations

Crystal structures of human and Staphylococcus aureus pyruvate carboxylase and molecular insights into the carboxyltransfer reaction.

Nat Struct Mol Biol 15 295-302 (2008)
Related entries: 3bg3, 3bg5

Cited: 69 times
EuropePMC logo PMID: 18297087

Abstract

Pyruvate carboxylase (PC) catalyzes the biotin-dependent production of oxaloacetate and has important roles in gluconeogenesis, lipogenesis, insulin secretion and other cellular processes. PC contains the biotin carboxylase (BC), carboxyltransferase (CT) and biotin-carboxyl carrier protein (BCCP) domains. We report here the crystal structures at 2.8-A resolution of full-length PC from Staphylococcus aureus and the C-terminal region (missing only the BC domain) of human PC. A conserved tetrameric association is observed for both enzymes, and our structural and mutagenesis studies reveal a previously uncharacterized domain, the PC tetramerization (PT) domain, which is important for oligomerization. A BCCP domain is located in the active site of the CT domain, providing the first molecular insights into how biotin participates in the carboxyltransfer reaction. There are dramatic differences in domain positions in the monomer and the organization of the tetramer between these enzymes and the PC from Rhizobium etli.

Reviews - 3bg9 mentioned but not cited (1)

Articles - 3bg9 mentioned but not cited (2)

  1. The dipeptidyl peptidase IV inhibitors vildagliptin and K-579 inhibit a phospholipase C: a case of promiscuous scaffolds in proteins. Chakraborty S, Rendón-Ramírez A, Ásgeirsson B, Dutta M, Ghosh AS, Oda M, Venkatramani R, Rao BJ, Dandekar AM, Goñi FM. F1000Res 2 286 (2013)
  2. Expanding the genetic spectrum of the pyruvate carboxylase deficiency with novel missense, deep intronic and structural variants. Tsygankova P, Bychkov I, Minzhenkova M, Pechatnikova N, Bessonova L, Buyanova G, Naumchik I, Beskorovainiy N, Tabakov V, Itkis Y, Shilova N, Zakharova E. Mol Genet Metab Rep 32 100889 (2022)


Reviews citing this publication (11)

  1. Regulation of pyruvate metabolism and human disease. Gray LR, Tompkins SC, Taylor EB. Cell Mol Life Sci 71 2577-2604 (2014)
  2. Structure, mechanism and regulation of pyruvate carboxylase. Jitrapakdee S, St Maurice M, Rayment I, Cleland WW, Wallace JC, Attwood PV. Biochem J 413 369-387 (2008)
  3. Structure and function of biotin-dependent carboxylases. Tong L. Cell Mol Life Sci 70 863-891 (2013)
  4. Fatty acid biosynthesis in actinomycetes. Gago G, Diacovich L, Arabolaza A, Tsai SC, Gramajo H. FEMS Microbiol Rev 35 475-497 (2011)
  5. Enzymes involved in l-lactate metabolism in humans. Adeva M, González-Lucán M, Seco M, Donapetry C. Mitochondrion 13 615-629 (2013)
  6. The enzymes of biotin dependent CO₂ metabolism: what structures reveal about their reaction mechanisms. Waldrop GL, Holden HM, St Maurice M. Protein Sci 21 1597-1619 (2012)
  7. Roles of pyruvate carboxylase in human diseases: from diabetes to cancers and infection. Lao-On U, Attwood PV, Jitrapakdee S. J Mol Med (Berl) 96 237-247 (2018)
  8. Allosteric regulation of the biotin-dependent enzyme pyruvate carboxylase by acetyl-CoA. Adina-Zada A, Zeczycki TN, St Maurice M, Jitrapakdee S, Cleland WW, Attwood PV. Biochem Soc Trans 40 567-572 (2012)
  9. Functionally diverse biotin-dependent enzymes with oxaloacetate decarboxylase activity. Lietzan AD, St Maurice M. Arch Biochem Biophys 544 75-86 (2014)
  10. Nearly 50 years in the making: defining the catalytic mechanism of the multifunctional enzyme, pyruvate carboxylase. Menefee AL, Zeczycki TN. FEBS J 281 1333-1354 (2014)
  11. Emerging chemical tools and techniques for tracking biological manganese. Das S, Khatua K, Rakshit A, Carmona A, Sarkar A, Bakthavatsalam S, Ortega R, Datta A. Dalton Trans 48 7047-7061 (2019)

Articles citing this publication (55)

  1. The cyclic dinucleotide c-di-AMP is an allosteric regulator of metabolic enzyme function. 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. Cell 158 1389-1401 (2014)
  2. Crystal structure of the alpha(6)beta(6) holoenzyme of propionyl-coenzyme A carboxylase. Huang CS, Sadre-Bazzaz K, Shen Y, Deng B, Zhou ZH, Tong L. Nature 466 1001-1005 (2010)
  3. A symmetrical tetramer for S. aureus pyruvate carboxylase in complex with coenzyme A. Yu LP, Xiang S, Lasso G, Gil D, Valle M, Tong L. Structure 17 823-832 (2009)
  4. Crystal structure of biotin carboxylase in complex with substrates and implications for its catalytic mechanism. Chou CY, Yu LP, Tong L. J Biol Chem 284 11690-11697 (2009)
  5. c-di-AMP modulates Listeria monocytogenes central metabolism to regulate growth, antibiotic resistance and osmoregulation. Whiteley AT, Garelis NE, Peterson BN, Choi PH, Tong L, Woodward JJ, Portnoy DA. Mol Microbiol 104 212-233 (2017)
  6. Crystal structure of the 500-kDa yeast acetyl-CoA carboxylase holoenzyme dimer. Wei J, Tong L. Nature 526 723-727 (2015)
  7. An unanticipated architecture of the 750-kDa α6β6 holoenzyme of 3-methylcrotonyl-CoA carboxylase. Huang CS, Ge P, Zhou ZH, Tong L. Nature 481 219-223 (2011)
  8. Early evolution of the biotin-dependent carboxylase family. Lombard J, Moreira D. BMC Evol Biol 11 232 (2011)
  9. Insight into the carboxyl transferase domain mechanism of pyruvate carboxylase from Rhizobium etli. Zeczycki TN, St Maurice M, Jitrapakdee S, Wallace JC, Attwood PV, Cleland WW. Biochemistry 48 4305-4313 (2009)
  10. Crystal structure of urea carboxylase provides insights into the carboxyltransfer reaction. Fan C, Chou CY, Tong L, Xiang S. J Biol Chem 287 9389-9398 (2012)
  11. Inhibitors of Pyruvate Carboxylase. Zeczycki TN, Maurice MS, Attwood PV. Open Enzym Inhib J 3 8-26 (2010)
  12. Cryo-EM analysis reveals new insights into the mechanism of action of pyruvate carboxylase. Lasso G, Yu LP, Gil D, Xiang S, Tong L, Valle M. Structure 18 1300-1310 (2010)
  13. Structural and functional studies of pyruvate carboxylase regulation by cyclic di-AMP in lactic acid bacteria. Choi PH, Vu TMN, Pham HT, Woodward JJ, Turner MS, Tong L. Proc Natl Acad Sci U S A 114 E7226-E7235 (2017)
  14. Structure and function of a single-chain, multi-domain long-chain acyl-CoA carboxylase. Tran TH, Hsiao YS, Jo J, Chou CY, Dietrich LE, Walz T, Tong L. Nature 518 120-124 (2015)
  15. Activation and inhibition of pyruvate carboxylase from Rhizobium etli. Zeczycki TN, Menefee AL, Jitrapakdee S, Wallace JC, Attwood PV, St Maurice M, Cleland WW. Biochemistry 50 9694-9707 (2011)
  16. Probing the catalytic roles of Arg548 and Gln552 in the carboxyl transferase domain of the Rhizobium etli pyruvate carboxylase by site-directed mutagenesis. Duangpan S, Jitrapakdee S, Adina-Zada A, Byrne L, Zeczycki TN, St Maurice M, Cleland WW, Wallace JC, Attwood PV. Biochemistry 49 3296-3304 (2010)
  17. Insights into the carboxyltransferase reaction of pyruvate carboxylase from the structures of bound product and intermediate analogs. Lietzan AD, St Maurice M. Biochem Biophys Res Commun 441 377-382 (2013)
  18. An isotope-coded fluorogenic cross-linker for high-performance target identification based on photoaffinity labeling. Tomohiro T, Morimoto S, Shima T, Chiba J, Hatanaka Y. Angew Chem Int Ed Engl 53 13502-13505 (2014)
  19. Quaternary structure of the oxaloacetate decarboxylase membrane complex and mechanistic relationships to pyruvate carboxylases. Balsera M, Buey RM, Li XD. J Biol Chem 286 9457-9467 (2011)
  20. Single-residue posttranslational modification sites at the N-terminus, C-terminus or in-between: To be or not to be exposed for enzyme access. Sirota FL, Maurer-Stroh S, Eisenhaber B, Eisenhaber F. Proteomics 15 2525-2546 (2015)
  21. Structural and biochemical studies on the regulation of biotin carboxylase by substrate inhibition and dimerization. Chou CY, Tong L. J Biol Chem 286 24417-24425 (2011)
  22. Structural insights on pathogenic effects of novel mutations causing pyruvate carboxylase deficiency. Monnot S, Serre V, Chadefaux-Vekemans B, Aupetit J, Romano S, De Lonlay P, Rival JM, Munnich A, Steffann J, Bonnefont JP. Hum Mutat 30 734-740 (2009)
  23. The three-dimensional structure of the biotin carboxylase-biotin carboxyl carrier protein complex of E. coli acetyl-CoA carboxylase. Broussard TC, Kobe MJ, Pakhomova S, Neau DB, Price AE, Champion TS, Waldrop GL. Structure 21 650-657 (2013)
  24. Probing the allosteric activation of pyruvate carboxylase using 2',3'-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate as a fluorescent mimic of the allosteric activator acetyl CoA. Adina-Zada A, Hazra R, Sereeruk C, Jitrapakdee S, Zeczycki TN, St Maurice M, Cleland WW, Wallace JC, Attwood PV. Arch Biochem Biophys 509 117-126 (2011)
  25. A substrate-induced biotin binding pocket in the carboxyltransferase domain of pyruvate carboxylase. Lietzan AD, St Maurice M. J Biol Chem 288 19915-19925 (2013)
  26. Quantitative and qualitative 2D electrophoretic analysis of differentially expressed mitochondrial proteins from five mouse organs. Techritz S, Lützkendorf S, Bazant E, Becker S, Klose J, Schuelke M. Proteomics 13 179-195 (2013)
  27. A unified molecular mechanism for the regulation of acetyl-CoA carboxylase by phosphorylation. Wei J, Zhang Y, Yu TY, Sadre-Bazzaz K, Rudolph MJ, Amodeo GA, Symington LS, Walz T, Tong L. Cell Discov 2 16044 (2016)
  28. Characterizing the importance of the biotin carboxylase domain dimer for Staphylococcus aureus pyruvate carboxylase catalysis. Yu LP, Chou CY, Choi PH, Tong L. Biochemistry 52 488-496 (2013)
  29. Functional conformations for pyruvate carboxylase during catalysis explored by cryoelectron microscopy. Lasso G, Yu LP, Gil D, Lázaro M, Tong L, Valle M. Structure 22 911-922 (2014)
  30. Selectivity in post-translational biotin addition to five human carboxylases. Ingaramo M, Beckett D. J Biol Chem 287 1813-1822 (2012)
  31. A C-terminal phosphatase module conserved in vertebrate CMP-sialic acid synthetases provides a tetramerization interface for the physiologically active enzyme. Oschlies M, Dickmanns A, Haselhorst T, Schaper W, Stummeyer K, Tiralongo J, Weinhold B, Gerardy-Schahn R, von Itzstein M, Ficner R, Münster-Kühnel AK. J Mol Biol 393 83-97 (2009)
  32. Crystal structures of vertebrate dihydropyrimidinase and complexes from Tetraodon nigroviridis with lysine carbamylation: metal and structural requirements for post-translational modification and function. Hsieh YC, Chen MC, Hsu CC, Chan SI, Yang YS, Chen CJ. J Biol Chem 288 30645-30658 (2013)
  33. A distinct holoenzyme organization for two-subunit pyruvate carboxylase. Choi PH, Jo J, Lin YC, Lin MH, Chou CY, Dietrich LEP, Tong L. Nat Commun 7 12713 (2016)
  34. Joint Genomic and Proteomic Analysis Identifies Meta-Trait Characteristics of Virulent and Non-virulent Staphylococcus aureus Strains. Bonar EA, Bukowski M, Hydzik M, Jankowska U, Kedracka-Krok S, Groborz M, Dubin G, Akkerboom V, Miedzobrodzki J, Sabat AJ, Friedrich AW, Wladyka B. Front Cell Infect Microbiol 8 313 (2018)
  35. Mechanisms of inhibition of Rhizobium etli pyruvate carboxylase by L-aspartate. Sirithanakorn C, Adina-Zada A, Wallace JC, Jitrapakdee S, Attwood PV. Biochemistry 53 7100-7106 (2014)
  36. My favorite pyruvate carboxylase. Wallace JC. IUBMB Life 62 535-538 (2010)
  37. Purification, crystallization and preliminary crystallographic analysis of biotin protein ligase from Staphylococcus aureus. Pendini NR, Polyak SW, Booker GW, Wallace JC, Wilce MC. Acta Crystallogr Sect F Struct Biol Cryst Commun 64 520-523 (2008)
  38. Roles of Arg427 and Arg472 in the binding and allosteric effects of acetyl CoA in pyruvate carboxylase. Adina-Zada A, Sereeruk C, Jitrapakdee S, Zeczycki TN, St Maurice M, Cleland WW, Wallace JC, Attwood PV. Biochemistry 51 8208-8217 (2012)
  39. Structure and substrate selectivity of the 750-kDa α6β6 holoenzyme of geranyl-CoA carboxylase. Jurado AR, Huang CS, Zhang X, Zhou ZH, Tong L. Nat Commun 6 8986 (2015)
  40. Systematic investigation of sequence and structural motifs that recognize ATP. Chen K, Wang D, Kurgan L. Comput Biol Chem 56 131-141 (2015)
  41. The role of biotin and oxamate in the carboxyltransferase reaction of pyruvate carboxylase. Lietzan AD, Lin Y, St Maurice M. Arch Biochem Biophys 562 70-79 (2014)
  42. Allosteric regulation alters carrier domain translocation in pyruvate carboxylase. Liu Y, Budelier MM, Stine K, St Maurice M. Nat Commun 9 1384 (2018)
  43. Coordinating role of His216 in MgATP binding and cleavage in pyruvate carboxylase. Adina-Zada A, Jitrapakdee S, Wallace JC, Attwood PV. Biochemistry 53 1051-1058 (2014)
  44. Discovery, structure, and function of filamentous 3-methylcrotonyl-CoA carboxylase. Hu JJ, Lee JKJ, Liu YT, Yu C, Huang L, Aphasizheva I, Aphasizhev R, Zhou ZH. Structure 31 100-110.e4 (2023)
  45. Localization of inhibitory antibodies to the biotin domain of human pyruvate carboxylase. Arpornsuwan T, Carey KJ, Booker GW, Polyak SW, Wallace JC. Hybridoma (Larchmt) 31 305-313 (2012)
  46. Residues in the acetyl CoA binding site of pyruvate carboxylase involved in allosteric regulation. Choosangtong K, Sirithanakorn C, Adina-Zada A, Wallace JC, Jitrapakdee S, Attwood PV. FEBS Lett 589 2073-2079 (2015)
  47. Single-particle analysis of urea amidolyase reveals its molecular mechanism. Liu Y, Yuan B, Peng L, Zhao J, Cheng B, Huang Y, Zheng X, Zhou Y, Xiang S, Zhu L, Wu Y. Protein Sci 29 1242-1249 (2020)
  48. Allosteric Site at the Biotin Carboxylase Dimer Interface Mediates Activation and Inhibition in Staphylococcus aureus Pyruvate Carboxylase. Laseke AJ, Boram TJ, Schneider NO, Lohman JR, St Maurice M. Biochemistry 62 2632-2644 (2023)
  49. Anemoside B4, a new pyruvate carboxylase inhibitor, alleviates colitis by reprogramming macrophage function. Liang QH, Li QR, Chen Z, Lv LJ, Lin Y, Jiang HL, Wang KX, Xiao MY, Kang NX, Tu PF, Ji SL, Deng KJ, Gao HW, Zhang L, Li K, Ge F, Xu GQ, Yang SL, Liu YL, Xu QM. Inflamm Res (2023)
  50. Clinical, biochemical and molecular characterization of 12 patients with pyruvate carboxylase deficiency treated with triheptanoin. Lasio MLD, Leshinski AC, Ducich NH, Flore LA, Lehman A, Shur N, Jayakar PB, Hainline BE, Basinger AA, Wilson WG, Diaz GA, Erbe RW, Koeberl DD, Vockley J, Bedoyan JK. Mol Genet Metab 139 107605 (2023)
  51. Cryo-EM structures of human SPCA1a reveal the mechanism of Ca2+/Mn2+ transport into the Golgi apparatus. Chen Z, Watanabe S, Hashida H, Inoue M, Daigaku Y, Kikkawa M, Inaba K. Sci Adv 9 eadd9742 (2023)
  52. CryoEM structural exploration of catalytically active enzyme pyruvate carboxylase. López-Alonso JP, Lázaro M, Gil-Cartón D, Choi PH, Dodu A, Tong L, Valle M. Nat Commun 13 6185 (2022)
  53. Detection of Recombinant Proteins SOX2 and OCT4 Interacting in HEK293T Cells Using Real-Time Quantitative PCR. Kanayev D, Abilmazhenova D, Akhmetollayev I, Sekenova A, Ogay V, Kulyyassov A. Life (Basel) 13 107 (2022)
  54. In silico Analysis of Two Novel Variants in the Pyruvate Carboxylase (PC) Gene Associated with the Severe Form of PC Deficiency. Maryami F, Rismani E, Davoudi-Dehaghani E, Khalesi N, Talebi S, Mahdian R, Zeinali S. Iran Biomed J 27 307-319 (2023)
  55. Kinetic, Structural, and Mutational Analysis of Acyl-CoA Carboxylase From Thermobifida fusca YX. Shivaiah KK, Upton B, Nikolau BJ. Front Mol Biosci 7 615614 (2020)