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Pathway Description
Molybdenum Cofactor Biosynthesis
Arabidopsis thaliana
Category:
Metabolite Pathway
Sub-Category:
Metabolic
Created: 2017-02-08
Last Updated: 2025-12-08
Molybdenum cofactor biosynthesis is a pathway that begins in the mitochondrial matrix and ends in the cytosol by which GTP becomes molybdenum cofactor, a metal-containing prosthetic group common to nearly all molybdoenzymes. Such molybdenum enzymes play important roles in the regulation of the nitrogen, sulfur and carbon cycles . First, the enzyme GTP 3',8-cyclase, located in the mitochondrial matrix, catalyzes the conversion of GTP, S-adenosylmethionine, and a reduced electron acceptor to 3′,8-cH2GTP, L-methionine, 5'-deoxyadenosine, an oxidized electron acceptor, and a hydrogen ion with the help of a [4Fe-4S] cluster cofactor. Second, cyclic pyranopterin monophosphate (cPMP) synthase catalyzes the conversion of 3′,8-cH2GTP to cPMP and pyrophosphate. Next, ABC transporter of the mitochondrion 3 (ATM3) exports cPMP from the mitochondrial matrix into the cytosol where it is acted upon by molybdopterin (MPT) synthase. MPT synthase is a heterotetramer composed of 2 large and 2 small subunits. The two small subunits are thiocarboxylated by molydopterin synthase sulfurtransferase, and each transfers a sulfur to cPMP to generate the dithiolene in molybdopterin and releasing hydrogen ion in the process. The following enzyme in the pathway, molybdenum insertase is a two-domain protein that catalyzes the fourth and fifth reactions. The smaller C-terminal Cnx1G domain functions as a molybdopterin molybdotransferase and activates molybdopterin for molybdenum insertion. The product of this reaction, molybdopterin adenine dinucleotide (MPT-AMP), is then transferred to the larger N-terminal Cnx1E domain which exhibits molybdopterin adenylyltransferase activity and inserts molybdenum into the dithiolene of molybdopterin, creating molybdenum cofactor (Moco). Molybdenum insertase requires a divalent cation (e.g. magnesium) as a cofactor.
References
Molybdenum Cofactor Biosynthesis References
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Pubmed: 25941396
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Stallmeyer B, Nerlich A, Schiemann J, Brinkmann H, Mendel RR: Molybdenum co-factor biosynthesis: the Arabidopsis thaliana cDNA cnx1 encodes a multifunctional two-domain protein homologous to a mammalian neuroprotein, the insect protein Cinnamon and three Escherichia coli proteins. Plant J. 1995 Nov;8(5):751-62.
Pubmed: 8528286
Tabata S, Kaneko T, Nakamura Y, Kotani H, Kato T, Asamizu E, Miyajima N, Sasamoto S, Kimura T, Hosouchi T, Kawashima K, Kohara M, Matsumoto M, Matsuno A, Muraki A, Nakayama S, Nakazaki N, Naruo K, Okumura S, Shinpo S, Takeuchi C, Wada T, Watanabe A, Yamada M, Yasuda M, Sato S, de la Bastide M, Huang E, Spiegel L, Gnoj L, O'Shaughnessy A, Preston R, Habermann K, Murray J, Johnson D, Rohlfing T, Nelson J, Stoneking T, Pepin K, Spieth J, Sekhon M, Armstrong J, Becker M, Belter E, Cordum H, Cordes M, Courtney L, Courtney W, Dante M, Du H, Edwards J, Fryman J, Haakensen B, Lamar E, Latreille P, Leonard S, Meyer R, Mulvaney E, Ozersky P, Riley A, Strowmatt C, Wagner-McPherson C, Wollam A, Yoakum M, Bell M, Dedhia N, Parnell L, Shah R, Rodriguez M, See LH, Vil D, Baker J, Kirchoff K, Toth K, King L, Bahret A, Miller B, Marra M, Martienssen R, McCombie WR, Wilson RK, Murphy G, Bancroft I, Volckaert G, Wambutt R, Dusterhoft A, Stiekema W, Pohl T, Entian KD, Terryn N, Hartley N, Bent E, Johnson S, Langham SA, McCullagh B, Robben J, Grymonprez B, Zimmermann W, Ramsperger U, Wedler H, Balke K, Wedler E, Peters S, van Staveren M, Dirkse W, Mooijman P, Lankhorst RK, Weitzenegger T, Bothe G, Rose M, Hauf J, Berneiser S, Hempel S, Feldpausch M, Lamberth S, Villarroel R, Gielen J, Ardiles W, Bents O, Lemcke K, Kolesov G, Mayer K, Rudd S, Schoof H, Schueller C, Zaccaria P, Mewes HW, Bevan M, Fransz P: Sequence and analysis of chromosome 5 of the plant Arabidopsis thaliana. Nature. 2000 Dec 14;408(6814):823-6. doi: 10.1038/35048507.
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