Skip to main content
SpringerLink
Log in

The Role of the Pyranopterin Dithiolene Component of Moco in Molybdoenzyme Catalysis

  • Chapter
  • First Online:
Metallocofactors that Activate Small Molecules

Part of the book series: Structure and Bonding ((STRUCTURE,volume 179))

Abstract

An overview of the pyranopterin dithiolene (MPT) component of the molybdenum cofactor (Moco) and how MPT may contribute to enzymatic catalysis is presented. The chapter begins with a brief review of MPT and Moco biosynthesis and continues to explore the nature of what is arguably the most electronically complex ligand in biology. To explore this complexity, we have dissected MPT into its relevant molecular components. These include the redox-active ene-1,2-dithiolate (dithiolene) and pterin moieties, which are bridged by a pyran that may be found in ring-opened or ring-closed configurations. The various redox possibilities of MPT bound to Mo are presented, along with the electronic structure of the redox components. MPTs are found to display a remarkable conformational variance in pyranopterin Mo enzymes. This is discussed in terms of a relationship to enzyme function and the potential for the observed non-planer distortions to reflect different MPT oxidation and tautomeric states. The chapter ends with a series of case studies featuring model compounds that highlight how biomimetic small molecule studies have contributed to furthering our understanding of the roles this remarkable ligand plays in the catalytic cycles of the enzymes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Pritsos CA (2000) Cellular distribution, metabolism and regulation of the xanthine oxidoreductase enzyme system. Chem Biol Interact 129(1–2):195

    CAS  PubMed  Google Scholar 

  2. Rooseboom M, Commandeur JNM, Vermeulen NPE (2004) Enzyme-catalyzed activation of anticancer prodrugs. Pharmacol Rev 56(1):53

    Article  CAS  Google Scholar 

  3. Kotthaus J et al (2011) New prodrugs of the antiprotozoal drug pentamidine. ChemMedChem 6:2233–2242

    CAS  PubMed  Google Scholar 

  4. Havemeyer A et al (2010) Reduction of N-hydroxy-sulfonamides, Including N-hydroxy-valdecoxib, by the molybdenum-containing enzyme mARC. Drug Metab Dispos 38:1917–1921

    CAS  PubMed  Google Scholar 

  5. Mendel RR, Kruse T (2012) Cell biology of molybdenum in plants and humans. BBA-Mol Cell Res 1823(9):1568–1579

    CAS  Google Scholar 

  6. Mendel RR, Schwarz G (2011) Molybdenum cofactor biosynthesis in plants and humans. Coord Chem Rev 255(9-10):1145–1158

    CAS  Google Scholar 

  7. Kotthaus J et al (2011) Reduction of N(ω)-hydroxy-L-arginine by the mitochondrial amidoxime reducing component (mARC). Biochem J 433:383–391

    CAS  PubMed  Google Scholar 

  8. Sparacino-Watkins CE et al (2014) Nitrite reductase and nitric-oxide synthase activity of the mitochondrial molybdopterin enzymes mARC1 and mARC2. J Biol Chem 289(15):10345–10358

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Hille R, Hall J, Basu P (2014) The mononuclear molybdenum enzymes. Chem Rev 114(7):3963–4038

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Hille R (2002) Molybdenum enzymes containing the pyranopterin cofactor: an overview. Marcel Dekker, Inc, New York, pp 187–226

    Google Scholar 

  11. Berry CE, Hare JM (2004) Xanthine oxidoreductase and cardiovascular disease: molecular mechanisms and pathophysiological implications. J Physiol 555(3):589–606

    CAS  PubMed  Google Scholar 

  12. Reiss J (2000) Genetics of molybdenum cofactor deficiency. Hum Genet 106(2):157

    CAS  PubMed  Google Scholar 

  13. Stein BW, Kirk ML (2015) Electronic structure contributions to reactivity in xanthine oxidase family enzymes. J Biol Inorg Chem 20(2):183–194

    CAS  PubMed  Google Scholar 

  14. Kirk ML, Stein B (2013) The molybdenum enzymes. In: Jan R, Kenneth P (eds) Comprehensive inorganic chemistry II, 2nd edn. Elsevier, Amsterdam, pp 263–293

    Google Scholar 

  15. Jones RM, Inscore FE, Hille R, Kirk ML (1999) Freeze-quench magnetic circular dichroism spectroscopic study of the “very rapid” intermediate in xanthine oxidase. Inorg Chem 38(22):4963–4970

    CAS  PubMed  Google Scholar 

  16. Hille R, Nishino T, Bittner F (2011) Molybdenum enzymes in higher organisms. Coord Chem Rev 255(9-10):1179–1205

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Hille R (2005) Molybdenum-containing hydroxylases. Arch Biochem Biophys 433(1):107–116

    CAS  PubMed  Google Scholar 

  18. Hille R (1997) Mechanistic aspects of the mononuclear molybdenum enzymes. J Biol Inorg Chem 2(6):804–809

    CAS  Google Scholar 

  19. Mtei RP et al (2011) Spectroscopic and electronic structure studies of a dimethyl sulfoxide reductase catalytic intermediate: implications for electron- and atom-transfer reactivity. J Am Chem Soc 133(25):9762–9774

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Hemann C et al (2005) Spectroscopic and kinetic studies of Arabidopsis thaliana sulfite oxidase: nature of the redox-active orbital and electronic structure contributions to catalysis. J Am Chem Soc 127(47):16567

    CAS  PubMed  Google Scholar 

  21. Yang J et al (2015) Oxyl and hydroxyl radical transfer in mitochondrial amidoxime reducing component-catalyzed nitrite reduction. J Am Chem Soc 137(16):5276–5279

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Maia L, Moura JG (2015) Nitrite reduction by molybdoenzymes: a new class of nitric oxide-forming nitrite reductases. J Biol Inorg Chem 20(2):403–433

    CAS  PubMed  Google Scholar 

  23. Hille R, Retey J, Bartlewski Hof U, Reichenbecher W, Schink B (1998) Mechanistic aspects of molybdenum containing enzymes. FEMS Microbiol Rev 22(5):489–501

    CAS  PubMed  Google Scholar 

  24. Hille R (1996) Structure and function of mononuclear molybdenum enzymes. J Biol Inorg Chem 1(5):397–404

    CAS  Google Scholar 

  25. Hille R (1996) The mononuclear molybdenum enzymes. Chem Rev 96(7):2757–2816

    CAS  PubMed  Google Scholar 

  26. Rothery RA, Stein B, Solomonson M, Kirk ML, Weiner JH (2012) Pyranopterin conformation defines the function of molybdenum and tungsten enzymes. Proc Natl Acad Sci U S A 109(37):14773–14778

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Kirk ML (2016) Spectroscopic and electronic structure studies of Mo model compounds and enzymes. In: Russ Hille CS, Kirk ML (eds) Molybdenum and tungsten enzymes: spectroscopic and theoretical investigations, RSC metallobiology series no. 7, The Royal Society of Chemistry, Cambridge, pp 13–67

    Google Scholar 

  28. Pushie MJ, George GN (2011) Spectroscopic studies of molybdenum and tungsten enzymes. Coord Chem Rev 255(9–10):1055–1084

    CAS  Google Scholar 

  29. Schwarz G (2016) Molybdenum cofactor and human disease. Curr Opin Chem Biol 31:179–187

    CAS  PubMed  Google Scholar 

  30. Mendel RR, Leimkuhler S (2015) The biosynthesis of the molybdenum cofactors. J Biol Inorg Chem 20(2):337–347

    CAS  PubMed  Google Scholar 

  31. Maia LB, Moura JJG, Moura I (2015) Molybdenum and tungsten-dependent formate dehydrogenases. J Biol Inorg Chem 20(2):287–309

    CAS  PubMed  Google Scholar 

  32. Metz S, Thiel W (2011) Theoretical studies on the reactivity of molybdenum enzymes. Coord Chem Rev 255(9–10):1085–1103

    CAS  Google Scholar 

  33. Sugimoto H, Tsukube H (2008) Chemical analogues relevant to molybdenum and tungsten enzyme reaction centres toward structural dynamics and reaction diversity. Chem Soc Rev 37(12):2609–2619

    CAS  PubMed  Google Scholar 

  34. Niks D, Hille R (2018) Molybdenum- and tungsten-containing formate dehydrogenases and formylmethanofuran dehydrogenases: structure, mechanism and cofactor insertion. Protein Sci 28(1):111–122

    PubMed  Google Scholar 

  35. Kaufholdt D, Baillie C-K, Meinen R, Mendel RR, Hänsch R (2017) The molybdenum cofactor biosynthesis network: in vivo protein-protein interactions of an actin associated multi-protein complex. Front Plant Sci 8:1946

    PubMed  PubMed Central  Google Scholar 

  36. Johnson JL, Rajagopalan KV (1982) Structural and metabolic relationship between the molybdenum cofactor and urothione. Proc Natl Acad Sci U S A 79:6856–6860

    CAS  PubMed  PubMed Central  Google Scholar 

  37. Groves JT (2006) High-valent iron in chemical and biological oxidations. J Inorg Biochem 100(4):434–447

    CAS  PubMed  Google Scholar 

  38. Rittle J, Green MT (2010) Cytochrome P450 compound I: capture, characterization, and C-H bond activation kinetics. Science 330(6006):933–937

    CAS  PubMed  Google Scholar 

  39. Holt BTO et al (2009) Reaction coordinate of a functional model of tyrosinase: spectroscopic and computational characterization. J Am Chem Soc 131(18):6421–6438

    Google Scholar 

  40. Mirica LM et al (2005) Tyrosinase reactivity in a model complex: an alternative hydroxylation mechanism. Science 308(5730):1890–1892

    CAS  PubMed  Google Scholar 

  41. Schwarz G, Mendel RR, Ribbe MW (2009) Molybdenum cofactors, enzymes and pathways. Nature 460(7257):839–847

    CAS  Google Scholar 

  42. Weiss MC et al (2016) The physiology and habitat of the last universal common ancestor. Nat Microbiol 1(9):16116

    CAS  PubMed  Google Scholar 

  43. Leimkuhler S & Mendel R (2016) Molybdenum cofactor biosynthesis. In: Hille R, Schulzke C, Kirk ML (eds) Molybdenum and tungsten enzymes, RSC metallobiochemistry, vol 1, RSC, Cambridge, pp 100–111

    Google Scholar 

  44. Schwarz G, Mendel RR (2006) Molybdenum cofactor biosynthesis and molybdoenzymes. Annu Rev Plant Biol 57(1):623–647

    CAS  PubMed  Google Scholar 

  45. Llamas A, Otte T, Multhaup G, Mendel RR, Schwarz G (2006) The mechanism of nucleotide-assisted molybdenum insertion into molybdopterin – a novel route toward metal cofactor assembly. J Biol Chem 281(27):18343–18350

    CAS  PubMed  Google Scholar 

  46. Krausze J et al (2018) The functional principle of eukaryotic molybdenum insertases. Biochem J 475:1739–1753

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Krausze J et al (2017) Dimerization of the plant molybdenum insertase Cnx1E is required for synthesis of the molybdenum cofactor. Biochem J 474(1):163

    CAS  PubMed  Google Scholar 

  48. Sempombe J, Stein B, Kirk ML (2011) Spectroscopic and electronic structure studies probing covalency contributions to C-H bond activation and transition-state stabilization in xanthine oxidase. Inorg Chem 50(21):10919–10928

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Ilich P, Hille R (1999) Mechanism of formamide hydroxylation catalyzed by a molybdenum-dithiolene complex: a model for xanthine oxidase reactivity. J Phys Chem B 103(25):5406–5412

    CAS  Google Scholar 

  50. Fischer B, Enemark JH, Basu P (1998) A chemical approach to systematically designate the pyranopterin centers of molybdenum and tungsten enzymes and synthetic models. J Inorg Biochem 72:13–21

    CAS  PubMed  Google Scholar 

  51. Schwarz, G, Mendel RR (2006) Molybdenum cofactor biosynthesis and molybdoenzymes. Annu Rev Plant Biol 57(1):623–647

    CAS  PubMed  Google Scholar 

  52. Greatbanks SP, Hillier IH, Garner CD, Joule JA (1997) The relative stabilities of dihydropterins; a comment on the structure of Moco; the cofactor of the oxomolybdoenzymes. J Chem Soc Perkin Trans 2(8):1529–1534

    Google Scholar 

  53. Enemark JH, Garner CD (1997) The coordination chemistry and function of the molybdenum centres of the oxomolybdoenzymes. J Biol Inorg Chem 2(6):817–822

    CAS  Google Scholar 

  54. Burgmayer SJN, Pearsall DL, Blaney SM, Moore EM, Sauk-Schubert C (2004) Redox reactions of the pyranopterin system of the molybdenum cofactor. J Biol Inorg Chem 9(1):59–66

    Google Scholar 

  55. Basu P, Burgmayer SJN (2011) Pterin chemistry and its relationship to the molybdenum cofactor. Coord Chem Rev 255(9‚10):1016–1038

    CAS  PubMed  PubMed Central  Google Scholar 

  56. Matz KG, Mtei RP, Rothstein R, Kirk ML, Burgmayer SJN (2011) Study of molybdenum(4+) quinoxalyldithiolenes as models for the noninnocent pyranopterin in the molybdenum cofactor. Inorg Chem 50(20):9804–9815

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Matz KG, Mtei RP, Leung B, Burgmayer SJN, Kirk ML (2010) Noninnocent dithiolene ligands: a new oxomolybdenum complex possessing a donor acceptor dithiolene ligand. J Am Chem Soc 132(23):7830–7831

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Burgmayer SJN et al (2007) Synthesis, characterization, and spectroscopy of model molybdopterin complexes. J Inorg Biochem 101(11-12):1601–1616

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Kirk ML (2016) Spectroscopic and electronic structure studies of Mo model compounds and enzymes. In: Molybdenum and tungsten enzymes: spectroscopic and theoretical investigations, vol 3, Molybdenum and tungsten enzymes, The Royal Society of Chemistry, London, pp 13–67

    Google Scholar 

  60. Adamson H et al (2015) Electrochemical evidence that pyranopterin redox chemistry controls the catalysis of YedY, a mononuclear Mo enzyme. Proc Natl Acad Sci U S A 112(47):14506–14511

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Hille R, Anderson RF (1991) Electron transfer in milk xanthine oxidase as studied by pulse radiolysis. J Biol Chem 266(9):5608–5615

    CAS  PubMed  Google Scholar 

  62. Bertero MG et al (2003) Insights into the respiratory electron transfer pathway from the structure of nitrate reductase A. Nat Struct Biol 10(9):681–687

    CAS  PubMed  Google Scholar 

  63. Kloer DP, Hagel C, Heider J, Schulz GE (2006) Crystal structure of ethylbenzene dehydrogenase from Aromatoleum aromaticum. Structure 14(9):1377–1388

    CAS  PubMed  Google Scholar 

  64. Jormakka M, Richardson D, Byrne B, Iwata S (2004) Architecture of NarGH reveals a structural classification of Mo-bisMGD enzymes. Structure 12(1):95–104

    CAS  PubMed  Google Scholar 

  65. Dietzel U et al (2009) Mechanism of substrate and inhibitor binding of rhodobacter capsulatus xanthine dehydrogenase. J Biol Chem 284(13):8759–8767

    Google Scholar 

  66. Enroth C et al (2000) Crystal structures of bovine milk xanthine dehydrogenase and xanthine oxidase: structure-based mechanism of conversion. Proc Natl Acad Sci U S A 97(20):10723–10728

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Leimkuhler S, Hodson R, George GN, Rajagopalan KV (2003) Recombinant Rhodobacter capsulatus xanthine dehydrogenase, a useful model system for the characterization of protein variants leading to xanthinuria I in humans. J Biol Chem 278(23):20802–20811

    PubMed  Google Scholar 

  68. Truglio J et al (2002) Crystal structures of the active and alloxanthine-inhibited forms of xanthine dehydrogenase from Rhodobacter capsulatus. Structure 10(1):115–125

    CAS  PubMed  Google Scholar 

  69. Westcott BL, Gruhn NE, Enemark JH (1998) Evaluation of molybdenum-sulfur interactions in molybdoenzyme model complexes by gas-phase photoelectron spectroscopy. The “electronic buffer” effect. J Am Chem Soc 120(14):3382–3386

    CAS  Google Scholar 

  70. Inscore FE et al (2006) Understanding the origin of metal-sulfur vibrations in an oxo-molybdenum dithiolene complex: relevance to sulfite oxidase. Inorg Chem 45(3):967

    CAS  PubMed  Google Scholar 

  71. Hille R (1991) Electron transfer within xanthine oxidase: a solvent kinetic isotope effect study. Biochemistry 30(35):8522–8529

    CAS  PubMed  Google Scholar 

  72. Hille R, Massey V (1981) Studies on the oxidative half-reaction of xanthine oxidase. J Biol Chem 256(17):9090–9095

    CAS  PubMed  Google Scholar 

  73. Dong C, Yang J, Leimkühler S, Kirk ML (2014) Pyranopterin dithiolene distortions relevant to electron transfer in xanthine oxidase/dehydrogenase. Inorg Chem 53(14):7077–7079

    CAS  PubMed  PubMed Central  Google Scholar 

  74. Gray HB, Winkler JR (2005) Long-range electron transfer. Proc Natl Acad Sci U S A 102(10):3534

    CAS  PubMed  PubMed Central  Google Scholar 

  75. Kirk ML et al (2013) Superexchange contributions to distance dependence of electron transfer/transport: exchange and electronic coupling in oligo(para-phenylene)- and oligo(2,5-thiophene)-bridged-donor-bridge acceptor biradical complexes. J Am Chem Soc 135(45):17144–17154

    CAS  PubMed  Google Scholar 

  76. Mtei RP et al (2011) A valence bond description of dizwitterionic dithiolene character in an oxomolybdenum–bis(dithione) complex. Eur J Inorg Chem 2011(36):5467–5470

    CAS  PubMed  PubMed Central  Google Scholar 

  77. Stiefel EI, Eisenberg R, Rosenberg R, Gray H (1966) Characterization and electronic structures of six-coordinate trigonal-prismatic complexes. J Am Chem Soc 88(13):2956–2966

    CAS  Google Scholar 

  78. Fourmigué M, Domercq B (1998) A non-innocent ligand in coordination chemistry: the dithiolene complexes. Actualite Chim 11–12:9–13

    Google Scholar 

  79. Wang K, McConnachie JM, Stiefel EI (1999) Syntheses of metal dithiolene complexes from thiometalates by induced internal redox reactions. Inorg Chem 38(19):4334–4341

    CAS  Google Scholar 

  80. Helton ME, Gruhn NE, McNaughton R, Kirk ML (2000) Control of oxo-molybdenum reduction and ionization potentials by dithiolate donors. Inorg Chem 39(11):2273–2278

    CAS  PubMed  Google Scholar 

  81. Harmer MA et al (1986) Ligand and induced internal redox processes in Mo-S and W-S systems. Polyhedron 5(1–2):341–347

    CAS  Google Scholar 

  82. Stiefel EI (1998) Transition metal sulfur chemistry and its relevance to molybdenum and tungsten enzymes. Pure Appl Chem 70(4):889–896

    CAS  Google Scholar 

  83. Helton ME, Gebhart NL, Davies S, Garner CD, Kirk ML (2000) Thermally driven intramolecular charge transfer in an oxo-molybdenum dithiolate complex. J Am Chem Soc. Manuscript in Preparation

    Google Scholar 

  84. Ray K, George SD, Solomon EI, Wieghardt K, Neese F (2007) Description of the ground-state covalencies of the bis(dithiolato) transition-metal complexes from X-ray absorption spectroscopy and time-dependent density-functional calculations. Chemistry 13(10):2783–2797

    CAS  PubMed  Google Scholar 

  85. Kirk ML, Helton ME, RL MN (eds) (2004) The electronic structure and spectroscopy of metallo-dithiolene complexes, vol 52. John Wiley and Sons, Inc, Hoboken, pp 111–212

    Google Scholar 

  86. Yang J, Mogesa B, Basu P, Kirk ML (2016) Large ligand folding distortion in an oxomolybdenum donor acceptor complex. Inorg Chem 55(2):785–793

    CAS  PubMed  Google Scholar 

  87. Sugimoto H et al (2010) Monooxomolybdenum(VI) complexes possessing olefinic dithiolene ligands: probing Mo-S covalency contributions to electron transfer in dimethyl sulfoxide reductase family molybdoenzymes. Inorg Chem 49(12):5368–5370

    CAS  PubMed  PubMed Central  Google Scholar 

  88. McNaughton RL, Lim BS, Knottenbelt SZ, Holm RH, Kirk ML (2008) Spectroscopic and electronic structure studies of symmetrized models for reduced members of the dimethylsulfoxide reductase enzyme family. J Am Chem Soc 130(14):4628–4636

    CAS  PubMed  Google Scholar 

  89. Kirk ML, McNaughton RL, Helton ME (2004) The electronic structure and spectroscopy of metallo-dithiolene complexes. In: Stiefel EI, Karlin KD (eds) Progress in inorganic chemistry: synthesis, properties, and applications, Progress in inorganic chemistry, vol 52, Wiley, Hoboken, pp 111–212

    Google Scholar 

  90. Inscore FE et al (1999) Spectroscopic evidence for a unique bonding interaction in oxo-molybdenum dithiolate complexes: implications for sigma electron transfer pathways in the pyranopterin dithiolate centers of enzymes. Inorg Chem 38(7):1401–1410

    CAS  Google Scholar 

  91. Yang J et al (2018) Ground state nuclear magnetic resonance chemical shifts predict charge-separated excited state lifetimes. Inorg Chem 57(21):13470–13476

    CAS  PubMed  Google Scholar 

  92. Yang J et al (2014) Ligand control of donor-acceptor excited-state lifetimes. Inorg Chem 53(10):4791–4793

    CAS  PubMed  Google Scholar 

  93. Chang C-SJ, Rai-Chaudhuri A, Lichtenberger DL, Enemark JH (1990) He I valence photoelectron spectra of oxomolybdenum (V) complexes containing diolato or alkoxide ligands. Polyhedron 9(15–16):1965–1973

    CAS  Google Scholar 

  94. Lalitha S, Manoharan PT (1989) X-ray photoelectron spectroscopic studies on some dithiolate complexes. J Electron Spectros Relat Phenom 49(1):61–75

    CAS  Google Scholar 

  95. Gleiter R, Spanget-Larsen J (1979). Top Curr Chem Spectrosc 86:139–195

    CAS  Google Scholar 

  96. Donahue JP, Holm RH (1998) 3,4-bis(l-adamantyl)-1,2-dithiete: the first structurally characterized dithiete unsupported by a ring or benzenoid frame. Acta Crystallogr C 54:1175–1178

    PubMed  Google Scholar 

  97. Davison A, Holm RH (1967) Metal complexes derived from cis-1,2-cyano-1,2-ethylenedithiolate and bis(trifluoromethyl)-1,2-dithiete. Inorg Synth 10:8–26

    CAS  Google Scholar 

  98. Frei F et al (2014) Ultrafast electronic and vibrational relaxations in mixed-ligand dithione-dithiolato Ni, Pd, and Pt complexes. Dalton Trans 43(47):17666–17676

    CAS  PubMed  Google Scholar 

  99. Espa D et al (2014) Role of the acceptor in tuning the properties of metal [M (II)= Ni, Pd, Pt] dithiolato/dithione (donor/acceptor) second-order nonlinear chromophores: combined experimental and theoretical studies. Inorg Chem 53(2):1170–1183

    CAS  PubMed  Google Scholar 

  100. Deplano P, Pilia L, Espa D, Mercuri ML, Serpe A (2010) Square-planar d(8) metal mixed-ligand dithiolene complexes as second order nonlinear optical chromophores: structure/property relationship. Coord Chem Rev 254(13–14):1434–1447

    CAS  Google Scholar 

  101. Perera E, Basu P (2009) Synthesis, characterization and structure of a low coordinate desoxomolybdenum cluster stabilized by a dithione ligand. Dalton Trans (25):5023–5028

    Google Scholar 

  102. Sproules S et al (2009) Characterization and electronic structures of five members of the electron transfer series [Re(benzene-1,2-dithiolato)(3)](z) (z=1+,0,1-,2-,3-): a spectroscopic and density functional theoretical study. Inorg Chem 48(23):10926–10941

    CAS  PubMed  Google Scholar 

  103. Stein BW et al (2018) Vibrational control of covalency effects related to the active sites of molybdenum enzymes. J Am Chem Soc. Accepted for Publication

    Google Scholar 

  104. Pauff JM, Cao H, Hille R (2009) Substrate orientation and catalysis at the molybdenum site in xanthine oxidase crystal structures in complex with xanthine and lumazine. J Biol Chem 284(13):8751–8758

    Google Scholar 

  105. Hemann C, Ilich P, Stockert AL, Choi EY, Hille R (2005) Resonance Raman studies of xanthine oxidase: the reduced enzyme – product complex with violapterin. J Phys Chem B 109(7):3023–3031

    CAS  PubMed  Google Scholar 

  106. Hemann C, Ilich P, Hille R (2003) Vibrational spectra of lumazine in water at pH 2-13: Ab initio calculation and FTIR/Raman spectra. J Phys Chem B 107(9):2139–2155

    CAS  Google Scholar 

  107. Davis M, Olson J, Palmer G (1984) The reaction of xanthine oxidase with lumazine: characterization of the reductive half-reaction. J Biol Chem 259(6):3526–3533

    CAS  PubMed  Google Scholar 

  108. Dong C, Yang J, Reschke S, Leimkühler S, Kirk ML (2017) Vibrational probes of molybdenum cofactor–protein interactions in xanthine dehydrogenase. Inorg Chem 56(12):6830–6837

    CAS  PubMed  Google Scholar 

  109. Qiu D, Kilpatrick LT, Kitajima N, Spiro TG (1994) Modeling blue copper protein resonance Raman spectra with thiolate-Cu(II) complexes of a sterically hindered tris(pyrazolyl)borate. J Am Chem Soc 116(6):2585–2590

    CAS  Google Scholar 

  110. Garton SD et al (2000) Resonance Raman characterization of biotin sulfoxide reductase: comparing oxomolybdenum enzymes in the Me2SO reductase family. J Biol Chem 275(10):6798–6805

    CAS  PubMed  Google Scholar 

  111. Johnson MK, Garton SD, Oku H (1997) Resonance Raman as a direct probe for the catalytic mechanism of molybdenum oxotransferases. J Biol Inorg Chem 2(6):797–803

    CAS  Google Scholar 

  112. Garton SD et al (1997) Active site structures and catalytic mechanism of Rhodobacter sphaeroides dimethyl sulfoxide reductase as revealed by resonance Raman spectroscopy. J Am Chem Soc 119(52):12906–12916

    CAS  Google Scholar 

  113. Johnson MK (ed) (2004) Vibrational spectra of dithiolene complexes, vol 52, John Wiley and Sons, Inc., Hoboken, pp 213–266

    Google Scholar 

  114. Rajagopalan K (1991) Novel aspects of the biochemistry of the molybdenum cofactor. Adv Enzymol Relat Areas Mol Biol 64:215–290

    CAS  PubMed  Google Scholar 

  115. Hille R, Massey V (1982) The presence of a reducible disulfide bond in milk xanthine oxidase. J Biol Chem 257(15):8898–8901

    CAS  PubMed  Google Scholar 

  116. Youngblut MD et al (2016) Perchlorate reductase is distinguished by active site aromatic gate residues. J Biol Chem 291(17):9190–9202

    CAS  PubMed  PubMed Central  Google Scholar 

  117. Jacques JGJ et al (2014) Reductive activation in periplasmic nitrate reductase involves chemical modifications of the Mo-cofactor beyond the first coordination sphere of the metal ion. BBA-Bioenergetics 1837(2):277–286

    CAS  PubMed  Google Scholar 

  118. Ceccaldi P et al (2015) Reductive activation of E. coli respiratory nitrate reductase. BBA-Bioenergetics 1847(10):1055–1063

    CAS  PubMed  Google Scholar 

  119. Gardlik S, Rajagopalan K (1991) Oxidation of molybdopterin in sulfite oxidase by ferricyanide-effect on electron transfer activities. J Biol Chem 266(8):4889–4895

    CAS  PubMed  Google Scholar 

  120. Gardlik S, Rajagopalan KV (1990) The state of reduction of molybdopterin in xanthine-oxidase and sulfite oxidase. J Biol Chem 265(22):13047–13054

    CAS  PubMed  Google Scholar 

  121. Karber LG, Dryhurst G (1984) Electrochemical oxidation of 5-methyl-5,6,7,8-tetrahydropterin. J Electroanal Chem 160(1–2):141–157

    CAS  Google Scholar 

  122. Karber LG, Dryhurst G (1982) Electrochemistry of 6-methyl-5,6,7,8-tetrahydropterin. J Electroanal Chem 136(2):271–289

    CAS  Google Scholar 

  123. Egeserpkenci D, Raghavan R, Dryhurst G (1983) Oxidation of methylated tetrahydropterins – structure of the initial quinonoid-dihydropterin intermediate. Bioelectrochem Bioenerg 10(4):357–376

    CAS  Google Scholar 

  124. Dryhurst G, Raghavan R, Egeserpkenci D, Karber LG (1982) Electrochemistry of reduced pterin cofactors. Adv Chem Ser (201):457–487

    Google Scholar 

  125. Raghavan R, Dryhurst G (1981) Redox chemistry of reduced pterin species. J Electroanal Chem 129(1–2):189–212

    CAS  Google Scholar 

  126. Bailey SW, Ayling JE (1983) 6,6-Dimethylpterins – stable quinoid dihydropterin substrate for dihydropteridine reductase and tetrahydropterin cofactor for phenylalanine hydroxylase. Biochemistry 22(8):1790–1798

    CAS  PubMed  Google Scholar 

  127. Brown DJ (1988) Fused pyrimidines. Wiley, New York

    Google Scholar 

  128. Pfleiderer W, Zondler H (1966) Pteridine, 31. Synthese und Eigenschaften blockierter 7.8-Dihydro-pterine. Chemische Berichte-Recueil 99(9):3008

    CAS  Google Scholar 

  129. Randles D, Armarego WLF (1985) Reduced 6,6,8-trimethyllpterins – preparation, properties and enzymic reactivities with dihydropteridine reductase, phenylalanine hydroxylase, and tyrosine hydroxylase. Eur J Biochem 146(2):467–474

    CAS  PubMed  Google Scholar 

  130. Kappock TJ, Caradonna JP (1996) Pterin-dependent amino acid hydroxylases. Chem Rev 96(7):2659–2756

    CAS  PubMed  Google Scholar 

  131. Kemsley JN et al (2003) Spectroscopic and kinetic studies of PKU-inducing mutants of phenylalanine hydroxylase: Arg158Gln and Glu280Lys. J Am Chem Soc 125(19):5677–5686

    CAS  PubMed  Google Scholar 

  132. Stoll S et al (2010) Nitric oxide synthase stabilizes the tetrahydrobiopterin cofactor radical by controlling its protonation state. J Am Chem Soc 132(33):11812–11823

    CAS  PubMed  Google Scholar 

  133. Hurshman AR, Krebs C, Edmondson DE, Marletta MA (2003) Ability of tetrahydrobiopterin analogues to support catalysis by inducible nitric oxide synthase: formation of a pterin radical is required for enzyme activity. Biochemistry 42(45):13287–13303

    CAS  PubMed  Google Scholar 

  134. Marletta MA (1993) Nitric oxide synthase structure and mechanism. J Biol Chem 268(17):12231–12234

    CAS  PubMed  Google Scholar 

  135. Soyka R, Pfleiderer W, Prewo R (1990) Pteridines, 94. Synthesis and characteristics of 5,6-dihydro-6-(1,2,3-trihydroxypropyl)pteridines – covalent intramolecular adducts. Helv Chim Acta 73(4):808–826

    CAS  Google Scholar 

  136. Schircks B, Bieri JH, Viscontini M (1985) Pterinechemistry, 84. A new, regiospecific synthesis of L-biopterin. Helv Chim Acta 68(6):1639–1643

    CAS  Google Scholar 

  137. Dong C, Yang J, Leimkuhler S, Kirk ML (2014) Pyranopterin dithiolene distortions relevant to electron transfer in xanthine oxidase/dehydrogenase. Inorg Chem 53(14):7077–7079

    CAS  PubMed  PubMed Central  Google Scholar 

  138. Kappler U, Bailey S (2005) Molecular basis of intramolecular electron transfer in sulfite-oxidizing enzymes is revealed by high resolution structure of a heterodimeric complex of the catalytic molybdopterin subunit and a c-type cytochrome subunit. J Biol Chem 280(26):24999–25007

    CAS  PubMed  Google Scholar 

  139. Gisewhite DR et al (2018) Implications of pyran cyclization and pterin conformation on oxidized forms of the molybdenum cofactor. J Am Chem Soc 140(40):12808–12818

    CAS  PubMed  PubMed Central  Google Scholar 

  140. Sugimoto H et al (2016) A model for the active-site formation process in DMSO reductase family molybdenum enzymes involving oxido alcoholato and oxido thiolato molybdenum(VI) core structures. Inorg Chem 55(4):1542–1550

    CAS  PubMed  PubMed Central  Google Scholar 

  141. Spence J (1983) Modeling the molybdenum centers of the molybdenum hydroxylases. Coord Chem Rev 48(1):59–82

    CAS  Google Scholar 

  142. Pilato R, Stiefel E (1993) Bioinorganic catalysis. Marcel Dekker, New York, pp 131–188

    Google Scholar 

  143. Maia LB, Moura I, Moura JJG (2017) Molybdenum and tungsten-containing enzymes: an overview. The Royal Society of Chemistry, Cambridge, pp 1–80

    Google Scholar 

  144. Enemark JH, Young CG (1993) Bioinorganic chemistry of pterin-containing molybdenum and tungsten enzymes. Adv Inorg Chem 40:1–88

    Google Scholar 

  145. Doonan CJ et al (2008) Electronic structure description of the cis-MoOS unit in models for molybdenum hydroxylases. J Am Chem Soc 130(1):55–65

    CAS  PubMed  Google Scholar 

  146. Enemark JH, Cooney JJA (2004) Synthetic analogues and reaction systems relevant to the molybdenum and tungsten oxotransferases. Chem Rev 104(2):1175–1200

    CAS  PubMed  Google Scholar 

  147. Holm RH (1987) Metal-centered oxygen atom transfer-reactions. Chem Rev 87(6):1401–1449

    CAS  Google Scholar 

  148. McNaughton RL, Helton ME, Rubie ND, Kirk ML (2000) The oxo-gate hypothesis and DMSO reductase: implications for a psuedo-sigma bonding interaction involved in enzymatic electron transfer. Inorg Chem 39(20):4386

    CAS  Google Scholar 

  149. McNaughton RL, Tipton AA, Rubie ND, Conry RR, Kirk ML (2000) Electronic structure studies of oxomolybdenum tetrathiolate complexes: origin of reduction potential differences and relationship to cysteine-molybdenum bonding in sulfite oxidase. Inorg Chem 39(25):5697–5706

    CAS  PubMed  Google Scholar 

  150. Peariso K, Helton ME, Duesler EN, Shadle SE, Kirk ML (2007) Sulfur K-edge spectroscopic investigation of second coordination sphere effects in oxomolybdenum-thiolates: relationship to molybdenum-cysteine covalency and electron transfer in sulfite oxidase. Inorg Chem 46(4):1259–1267

    CAS  PubMed  Google Scholar 

  151. Nemykin VN, Olsen JG, Perera E, Basu P (2006) Synthesis, molecular and electronic structure, and TDDFT and TDDFT-PCM study of the solvatochromic properties of (Me(2)Pipdt)Mo(CO)(4) complex (Me(2)Pipdt = N,N′-dimethylpiperazine-2,3-dithione). Inorg Chem 45(9):3557–3568

    Google Scholar 

  152. Boyde S, Garner CD (1991) Electrochemistry of tris(quinoxaline-2,3-dithiolato)molybdate(IV) in acidic solution: multi-electron ligand-based redox activity. J Chem Soc Dalton Trans 713–716

    Google Scholar 

  153. Armstrong EM et al (1993) Synthesis of cyclopentadienyl-ene-1,2-dithiolatocobalt complexes and coupled proton-electron transfer in a substituted quinoxalinyl derivative. Heterocycles 35(2):563–568

    CAS  Google Scholar 

  154. Dicks JP et al (2015) Synthesis, structure and redox properties of asymmetric (cyclopentadienyl)(ene-1,2-dithiolate)cobalt(III) complexes containing phenyl, pyridyl and pyrazinyl units. Eur J Inorg Chem 21:3550–3561

    Google Scholar 

  155. Hsu JK et al (1996) Direct conversion of alpha-substituted ketones to metallo-1,2-enedithiolates. Inorg Chem 35(16):4743–4751

    CAS  Google Scholar 

  156. Kaiwar SP, Vodacek A, Blough NV, Pilato RS (1997) Protonation-state-dependent luminescence and excited-state electron-transfer reactions of 2- and 4-pyridine (-ium)-substituted metallo-1,2-enedithiolates. J Am Chem Soc 119:9211–9214

    CAS  Google Scholar 

  157. VanHouten KA, Boggs CV, Pilato RS (1998) Synthesis and characterization of alpha-phosphorylated ketones: models for the molybdopterin precursor. Tetrahedron 54(37):10973–10986

    CAS  Google Scholar 

  158. Pilato RS et al (1993) Pterins, quinoxalines, and metallo-ene-dithiolates – synthetic approach to the molybdenum cofactor. ACS Symp Ser 535:83–97

    CAS  Google Scholar 

  159. Pilato RS et al (1991) Model complexes for molybdopterin-containing enzymes: preparation and crystallographic characterization of a molybdenum-ene-1-perthiolate-2-thiolate (trithiolate) complex. J Am Chem Soc 9372–9374

    CAS  Google Scholar 

  160. Fogeron T, Retailleau P, Chamoreau LM, Li Y, Fontecave M (2018) Pyranopterin related dithiolene molybdenum complexes as homogeneous catalysts for CO2 photoreduction. Angew Chem Int Ed 57(52):17033–17037

    CAS  Google Scholar 

  161. Porcher JP et al (2015) A bioinspired molybdenum complex as a catalyst for the photo- and electroreduction of protons. Angew Chem Int Ed 54(47):14090–14093

    CAS  Google Scholar 

  162. Gisewhite DR, Nagelski AL, Cummins DC, Yap GPA, Burgmayer SJN (2019). Modeling pyran formation in the molybdenum cofactor: protonation of quinoxalyl-dithiolene promoting pyran cyclization. Inorg Chem 58(8):5134–5144. https://doi.org/10.1021/acs.inorgchem.9b00194

    CAS  PubMed  PubMed Central  Google Scholar 

  163. Gisewhite D (2018) The molybdenum cofactor: modeling the Swiss army knife of metabolic diversity. PhD, Bryn Mawr College

    Google Scholar 

  164. Williams BR, Fu YC, Yap GPA, Burgmayer SJN (2012) Structure and reversible pyran formation in molybdenum pyranopterin dithiolene models of the molybdenum cofactor. J Am Chem Soc 134(48):19584–19587

    CAS  PubMed  PubMed Central  Google Scholar 

  165. Williams BR, Gisewhite D, Kalinsky A, Esmail A, Burgmayer SJN (2015) Solvent-dependent pyranopterin cyclization in molybdenum cofactor model complexes. Inorg Chem 54(17):8214–8222

    CAS  PubMed  PubMed Central  Google Scholar 

  166. Bray R, Adams B, Smith A, Bennett B, Bailey S (2000) Reversible dissociation of thiolate ligands from molybdenum in an enzyme of the dimethyl sulfoxide reductase family. Biochemistry 39(37):11258–11269

    CAS  PubMed  Google Scholar 

  167. Bell AF et al (2001) Active site heterogeneity in dimethyl sulfoxide reductase from Rhodobacter capsulatus revealed by Raman spectroscopy. Biochemistry 40(2):440–448

    CAS  PubMed  Google Scholar 

  168. George GN, Hilton J, Temple C, Prince RC, Rajagopalan KV (1999) Structure of the molybdenum site of dimethyl sulfoxide reductase. J Am Chem Soc 121:1256–1266

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry, Bryn Mawr College, Bryn Mawr, PA, USA

    Sharon J. Nieter Burgmayer

  2. Department of Chemistry and Chemical Biology, The University of New Mexico, Albuquerque, NM, USA

    Martin L. Kirk

Authors
  1. Sharon J. Nieter Burgmayer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Martin L. Kirk
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Sharon J. Nieter Burgmayer or Martin L. Kirk .

Editor information

Editors and Affiliations

  1. Departments of Molecular Biology & Biochemistry, and Chemistry, University of California, Irvine, CA, USA

    Markus W. Ribbe

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Nieter Burgmayer, S.J., Kirk, M.L. (2019). The Role of the Pyranopterin Dithiolene Component of Moco in Molybdoenzyme Catalysis. In: Ribbe, M. (eds) Metallocofactors that Activate Small Molecules. Structure and Bonding, vol 179. Springer, Cham. https://doi.org/10.1007/430_2019_31

Download citation

Publish with us

Policies and ethics

Search

Navigation