MetaCyc Enzyme: molybdopterin synthase

Gene: MOCS2 Accession Number: HS09033 (MetaCyc)

Synonyms: MOCO1, MPTS

Species: Homo sapiens

Subunit composition of molybdopterin synthase = [MOCS2]2[MOCS2]2
         molybdopterin synthase sulfur carrier subunit = MOCS2
         molybdopterin synthase catalytic subunit = MOCS2

cDNA clones of the two subunits of the human molybdopterin synthase were identified based on their similarity to the CnxG and CnxH proteins of the mold Aspergillus nidulans. Interestingly, it was found that the large and small subunits are both encoded from the same gene, by overlapping and shifted open reading frames, which is a highly unusual structure for eukaryotes [Sloan99, Hahnewald06].

The proteins were initially thought to be encoded from a bicistronic transcript [Stallmeyer99], but are now thought to be encoded from monocistronic transcripts.

As in other organisms, the smaller subunit of the enzyme (MOCS2A) is modified to contain a thiocarboxylate group at its C-terminus, which it subsequently donates to cyclic pyranopterin phosphate (precursor Z), converting it to molybdopterin. This modification is catalyzed by the MOCS3 adenylyltransferase/sulfurtransferase, which catalyzes both the adenylylation and the subsequent generation of the thiocarboxylate group [Matthies05].

The MOCS2A and MOCS2B subunits were purified after heterologous expression in Escherichia coli, and the separately purified subunits readily assemble into a functional MPT synthase tetramer [Leimkuhler03].

Mutations in this protein lead to molybdenum cofactor deficiency [Leimkuhler03, Reiss99, Johnson01a, Leimkuhler05, Hahnewald06].

Map Position: [53,821,807 <- 53,835,481]

Unification Links: ArrayExpress:O96007, ArrayExpress:O96033, Entrez-gene:4338, String:9606.ENSP00000380157

Gene-Reaction Schematic

Gene-Reaction Schematic

Created 20-Jun-2011 by Caspi R, SRI International

Enzymatic reaction of: molybdopterin synthase

Inferred from experiment

EC Number:

cyclic pyranopterin phosphate + 2 a thiocarboxylated small subunit of molybdopterin synthase + H2O → 2 a small subunit of molybdopterin synthase + molybdopterin + 4 H+

The direction shown, i.e. which substrates are on the left and right sides, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: molybdenum cofactor biosynthesis

Subunit of molybdopterin synthase: molybdopterin synthase sulfur carrier subunit

Synonyms: MOCS2A

Gene: MOCS2 Accession Number: HS09033 (MetaCyc)

Sequence Length: 13672/3 AAs

Molecular Weight: 9.755 kD (from nucleotide sequence)

Unification Links: Mint:MINT-1397621, Pride:O96033, Protein Model Portal:O96033, SMR:O96033, UniProt:O96033

Relationship Links: InterPro:IN-FAMILY:IPR003749, InterPro:IN-FAMILY:IPR010034, InterPro:IN-FAMILY:IPR012675, InterPro:IN-FAMILY:IPR016155, InterPro:IN-FAMILY:IPR028887, Pfam:IN-FAMILY:PF02597

Reactions known to consume the compound:

molybdenum cofactor biosynthesis :
a small subunit of molybdopterin synthase + ATP + H+ → a carboxy-adenylated small subunit of molybdopterin synthase + diphosphate

Reactions known to produce the compound:

molybdenum cofactor biosynthesis :
cyclic pyranopterin phosphate + 2 a thiocarboxylated small subunit of molybdopterin synthase + H2O → 2 a small subunit of molybdopterin synthase + molybdopterin + 4 H+

Subunit of molybdopterin synthase: molybdopterin synthase catalytic subunit

Synonyms: MOCS2B, MOCO1- B, molybdenum cofactor synthesis 2, molybdenum cofactor synthesis 2 large subunit MOSC2B

Gene: MOCS2 Accession Number: HS09033 (MetaCyc)

Molecular Weight: 20.944 kD (from nucleotide sequence)

Unification Links: PhosphoSite:O96007, PhylomeDB:O96007, Pride:O96007, Protein Model Portal:O96007, SMR:O96007, UniProt:O96007

Relationship Links: InterPro:IN-FAMILY:IPR003448, InterPro:IN-FAMILY:IPR028888, Panther:IN-FAMILY:PTHR23404:SF2, PDB:Structure:4AP8, Pfam:IN-FAMILY:PF02391

Citations: [Reiss99, Stallmeyer99, Sloan99, Feng98, Reiss98]


Schematic showing introns, exons and/or isoforms of MOCS2


Feng98: Feng G, Tintrup H, Kirsch J, Nichol MC, Kuhse J, Betz H, Sanes JR (1998). "Dual requirement for gephyrin in glycine receptor clustering and molybdoenzyme activity." Science 282(5392);1321-4. PMID: 9812897

Hahnewald06: Hahnewald R, Leimkuhler S, Vilaseca A, Acquaviva-Bourdain C, Lenz U, Reiss J (2006). "A novel MOCS2 mutation reveals coordinated expression of the small and large subunit of molybdopterin synthase." Mol Genet Metab 89(3);210-3. PMID: 16737835

Johnson01a: Johnson JL, Coyne KE, Rajagopalan KV, Van Hove JL, Mackay M, Pitt J, Boneh A (2001). "Molybdopterin synthase mutations in a mild case of molybdenum cofactor deficiency." Am J Med Genet 104(2);169-73. PMID: 11746050

Leimkuhler03: Leimkuhler S, Freuer A, Araujo JA, Rajagopalan KV, Mendel RR (2003). "Mechanistic studies of human molybdopterin synthase reaction and characterization of mutants identified in group B patients of molybdenum cofactor deficiency." J Biol Chem 278(28);26127-34. PMID: 12732628

Leimkuhler05: Leimkuhler S, Charcosset M, Latour P, Dorche C, Kleppe S, Scaglia F, Szymczak I, Schupp P, Hahnewald R, Reiss J (2005). "Ten novel mutations in the molybdenum cofactor genes MOCS1 and MOCS2 and in vitro characterization of a MOCS2 mutation that abolishes the binding ability of molybdopterin synthase." Hum Genet 117(6);565-70. PMID: 16021469

Matthies05: Matthies A, Nimtz M, Leimkuhler S (2005). "Molybdenum cofactor biosynthesis in humans: identification of a persulfide group in the rhodanese-like domain of MOCS3 by mass spectrometry." Biochemistry 44(21);7912-20. PMID: 15910006

Reiss98: Reiss J, Cohen N, Dorche C, Mandel H, Mendel RR, Stallmeyer B, Zabot MT, Dierks T (1998). "Mutations in a polycistronic nuclear gene associated with molybdenum cofactor deficiency." Nat Genet 20(1);51-3. PMID: 9731530

Reiss99: Reiss J, Dorche C, Stallmeyer B, Mendel RR, Cohen N, Zabot MT (1999). "Human molybdopterin synthase gene: genomic structure and mutations in molybdenum cofactor deficiency type B." Am J Hum Genet 64(3);706-11. PMID: 10053004

Sloan99: Sloan J, Kinghorn JR, Unkles SE (1999). "The two subunits of human molybdopterin synthase: evidence for a bicistronic messenger RNA with overlapping reading frames." Nucleic Acids Res 27(3);854-8. PMID: 9889283

Stallmeyer99: Stallmeyer B, Drugeon G, Reiss J, Haenni AL, Mendel RR (1999). "Human molybdopterin synthase gene: identification of a bicistronic transcript with overlapping reading frames." Am J Hum Genet 64(3);698-705. PMID: 10053003

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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