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Pathway Description
GTP Degradation and Molybdenum Cofactor Biosynthesis
Escherichia coli
Metabolic Pathway
GTP, produced in the nucleotide de novo biosyntheis pathway, interacts with a water molecule through a GTP cyclohydrolase resulting in a formate, hydrogen ion and a 7,8-dihydroneopterin 3'-triphosphate. The latter compound interacts with a water molecule through a dihydroneopterin triphosphate pyrophosphohydrolase resulting in the release of a pyrophosphate, a hydrogen ion and a 7,8-dihydroneopterin 3'-phosphate. The latter compound interacts with water spontaneously resulting in the release of a phosphate and a 7,8 dihydroneopterin. The latter compound interacts with a dihydroneopterin aldolase resulting in the release of a glycolaldehyde and a 6-hydroxymethyl-7,8-dihydropterin. This compound then is then diphosphorylated by reacting with a ATP driven 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase resulting in the release of a hydrogen ion, an AMP and 6-hydroxymethyl-7,8-dihydropterin diphosphate.
GTP interacts with a cyclic pyranopterin monophosphate synthase resulting in the release of a diphosphate and a cyclic pyranopterin phosphate. The latter compound interacts with a thiocarboxylated small subunit of molybdopterin synthase (a protein) and a water molecule through a molybdopterin synthase resulting in the release of 4 hydrogen ions, 2 small subunits of molybdopterin synthase and a molybdopterin. The molybdopterin interacts with an ATP and a hydrogen ion through a molybdopterin adenylyltransferase resulting in the release of a diphosphate and a molybdopterin adenine dinucleotide. The latter compound is then metabolized by a hydrogen ion and a molybdate through a molybdopterin molybdenumtransferase resulting in the release of an AMP, a water molecule and a molybdopterin cofactor.
The molybdopterin cofactor can procede to the guanylyl molybdenum cofactor biosynthesis pathway or it can be metabolized into a cytidylyl molybdenum cofactor by interacting with a CTP and a hydrogen ion through a molybdenym cofactor cytidylyltransferase resulting in the release of a pyrophosphate and a cytidyllyl molybdenum cofactor
References
GTP Degradation and Molybdenum Cofactor Biosynthesis References
Gutzke G, Fischer B, Mendel RR, Schwarz G: Thiocarboxylation of molybdopterin synthase provides evidence for the mechanism of dithiolene formation in metal-binding pterins. J Biol Chem. 2001 Sep 28;276(39):36268-74. doi: 10.1074/jbc.M105321200. Epub 2001 Jul 17.
Pubmed: 11459846
Iobbi-Nivol C, Leimkuhler S: Molybdenum enzymes, their maturation and molybdenum cofactor biosynthesis in Escherichia coli. Biochim Biophys Acta. 2013 Aug-Sep;1827(8-9):1086-101. doi: 10.1016/j.bbabio.2012.11.007. Epub 2012 Nov 29.
Pubmed: 23201473
Mendel RR, Hansch R: Molybdoenzymes and molybdenum cofactor in plants. J Exp Bot. 2002 Aug;53(375):1689-98.
Pubmed: 12147719
Mendel RR: Molybdenum: biological activity and metabolism. Dalton Trans. 2005 Nov 7;(21):3404-9. doi: 10.1039/b505527j. Epub 2005 Sep 26.
Pubmed: 16234918
Mendel RR, Bittner F: Cell biology of molybdenum. Biochim Biophys Acta. 2006 Jul;1763(7):621-35. doi: 10.1016/j.bbamcr.2006.03.013. Epub 2006 May 12.
Pubmed: 16784786
Mendel RR: Molybdenum cofactor of higher plants: biosynthesis and molecular biology. Planta. 1997 Dec;203(4):399-405. doi: 10.1007/s004250050206.
Pubmed: 9421926
Nichols JD, Xiang S, Schindelin H, Rajagopalan KV: Mutational analysis of Escherichia coli MoeA: two functional activities map to the active site cleft. Biochemistry. 2007 Jan 9;46(1):78-86. doi: 10.1021/bi061551q.
Pubmed: 17198377
Pitterle DM, Johnson JL, Rajagopalan KV: In vitro synthesis of molybdopterin from precursor Z using purified converting factor. Role of protein-bound sulfur in formation of the dithiolene. J Biol Chem. 1993 Jun 25;268(18):13506-9.
Pubmed: 8514783
Pitterle DM, Rajagopalan KV: The biosynthesis of molybdopterin in Escherichia coli. Purification and characterization of the converting factor. J Biol Chem. 1993 Jun 25;268(18):13499-505.
Pubmed: 8514782
Rajagopalan KV, Johnson JL: The pterin molybdenum cofactors. J Biol Chem. 1992 May 25;267(15):10199-202.
Pubmed: 1587808
Santamaria-Araujo JA, Fischer B, Otte T, Nimtz M, Mendel RR, Wray V, Schwarz G: The tetrahydropyranopterin structure of the sulfur-free and metal-free molybdenum cofactor precursor. J Biol Chem. 2004 Apr 16;279(16):15994-9. doi: 10.1074/jbc.M311815200. Epub 2004 Feb 3.
Pubmed: 14761975
Bermingham A, Derrick JP: The folic acid biosynthesis pathway in bacteria: evaluation of potential for antibacterial drug discovery. Bioessays. 2002 Jul;24(7):637-48. doi: 10.1002/bies.10114.
Pubmed: 12111724
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