D
IPR010505

Molybdenum cofactor biosynthesis protein A-like, twitch domain

InterPro entry
Short nameMoaA_twitch
Overlapping
homologous
superfamilies
 

Description

This entry represents the iron-sulfur cluster-binding twitch domain of GTP 3',8-cyclase, which is also known as molybdenum cofactor biosynthesis protein A (MoaA) in bacteria and archaea, molybdenum cofactor biosynthesis protein 1 (MOCS1) in most eukaryotes, and molybdenum cofactor biosynthesis enzyme CNX2 in plants
[5]
. They belong to a family of enzymes involved in the synthesis of metallo-cofactors (
IPR000385
). Each subunit of the MoaA dimer is comprised of an N-terminal SAM domain (
IPR007197
) that contains the [4Fe-4S] cluster typical for this family of enzymes, as well as an additional [4Fe-4S] cluster in the C-terminal domain that is unique to MoaA proteins, involved in substrate binding
[2]
. The unique Fe site of the C-terminal [4Fe-4S] cluster is thought to be involved in the binding and activation of 5'-GTP
[6]
.

Mutations in the human MoCF biosynthesis proteins MOCS1, MOCS2 or GEPH cause MoCF Deficiency type A (MOCOD), causing the loss of activity of MoCF-containing enzymes, resulting in neurological abnormalities and death
[3]
.

The majority of molybdenum-containing enzymes utilise a molybdenum cofactor (MoCF or Moco) consisting of a Mo atom coordinated via a cis-dithiolene moiety to molybdopterin (MPT). MoCF is ubiquitous in nature, and the pathway for MoCF biosynthesis is conserved in all three domains of life. MoCF-containing enzymes function as oxidoreductases in carbon, nitrogen, and sulphur metabolism
[1, 4]
.

References

1.Cell biology of molybdenum. Mendel RR, Bittner F. Biochim. Biophys. Acta 1763, 621-35, (2006). View articlePMID: 16784786

2.Crystal structure of the S-adenosylmethionine-dependent enzyme MoaA and its implications for molybdenum cofactor deficiency in humans. Hanzelmann P, Schindelin H. Proc. Natl. Acad. Sci. U.S.A. 101, 12870-5, (2004). View articlePMID: 15317939

3.Mutations in the molybdenum cofactor biosynthetic genes MOCS1, MOCS2, and GEPH. Reiss J, Johnson JL. Hum. Mutat. 21, 569-76, (2003). View articlePMID: 12754701

4.Molybdenum and tungsten in biology. Hille R. Trends Biochem. Sci. 27, 360-7, (2002). View articlePMID: 12114025

5.SPASM and twitch domains in S-adenosylmethionine (SAM) radical enzymes. Grell TA, Goldman PJ, Drennan CL. J. Biol. Chem. 290, 3964-71, (2015). View articlePMID: 25477505

6.Binding of 5'-GTP to the C-terminal FeS cluster of the radical S-adenosylmethionine enzyme MoaA provides insights into its mechanism. Hanzelmann P, Schindelin H. Proc. Natl. Acad. Sci. U.S.A. 103, 6829-34, (2006). View articlePMID: 16632608

Further reading

7. Mutational analysis of Escherichia coli MoeA: two functional activities map to the active site cleft. Nichols JD, Xiang S, Schindelin H, Rajagopalan KV. Biochemistry 46, 78-86, (2007). View articlePMID: 17198377

8. In vivo interactions between gene products involved in the final stages of molybdenum cofactor biosynthesis in Escherichia coli. Magalon A, Frixon C, Pommier J, Giordano G, Blasco F. J. Biol. Chem. 277, 48199-204, (2002). View articlePMID: 12372836

9. 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. Stallmeyer B, Nerlich A, Schiemann J, Brinkmann H, Mendel RR. Plant J. 8, 751-62, (1995). View articlePMID: 8528286

GO terms

Cross References

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