IntEnz

EC 1.20.4.1 - Arsenate reductase (glutathione/glutaredoxin)

IntEnz Enzyme Nomenclature
EC 1.20.4.1

Names

Reaction

• arsenate + glutathione + glutaredoxin = arsenite + a glutaredoxin-glutathione disulfide + H2O

Cofactor

• Mo cation

Comments:

The enzyme is part of a system for detoxifying arsenate. The substrate binds to a catalytic cysteine residue, forming a covalent thiolate—As(V) intermediate. A tertiary intermediate is then formed between the arsenic, the enzyme's cysteine, and a glutathione cysteine. This intermediate is reduced by glutaredoxin, which forms a dithiol with the glutathione, leading to the dissociation of arsenite. Thus reduction of As(V) is mediated by three cysteine residues: one in ArsC, one in glutathione, and one in glutaredoxin. Although the arsenite formed is more toxic than arsenate, it can be extruded from some bacteria by EC 7.3.2.7, arsenite-transporting ATPase; in other organisms, arsenite can be methylated by EC 2.1.1.137, arsenite methyltransferase, in a pathway that produces non-toxic organoarsenical compounds. cf. EC 1.20.4.4, arsenate reductase (thioredoxin).

Links to other databases

References

1. Gladysheva, T., Liu, J.Y. and Rosen, B.P.
   His-8 lowers the pK_a of the essential Cys-12 residue of the ArsC arsenate reductase of plasmid R773.
   J. Biol. Chem. 271 : 33256-33260 (1996). [PMID: 8969183]
2. Gladysheva, T.B., Oden, K.L. and Rosen, B.P.
   Properties of the arsenate reductase of plasmid R773.
   Biochemistry 33 : 7288-7293 (1994). [PMID: 8003492]
3. Holmgren, A. and Aslund, F.
   Glutaredoxin.
   Methods Enzymol. 252 : 283-292 (1995). [PMID: 7476363]
4. Krafft, T. and Macy, J.M.
   Purification and characterization of the respiratory arsenate reductase of Chrysiogenes arsenatis.
   Eur. J. Biochem. 255 : 647-653 (1998). [PMID: 9738904]
5. Martin, J.L.
   Thioredoxin - a fold for all reasons.
   Structure 3 : 245-250 (1995). [PMID: 7788290]
6. Radabaugh, T.R. and Aposhian, H.V.
   Enzymatic reduction of arsenic compounds in mammalian systems: reduction of arsenate to arsenite by human liver arsenate reductase.
   Chem. Res. Toxicol. 13 : 26-30 (2000). [PMID: 10649963]
7. Sato, T. and Kobayashi, Y.
   The ars operon in the skin element of Bacillus subtilis confers resistance to arsenate and arsenite.
   J. Bacteriol. 180 : 1655-1661 (1998). [PMID: 9537360]
8. Shi, J., Vlamis-Gardikas, V., Aslund, F., Holmgren, A. and Rosen, B.P.
   Reactivity of glutaredoxins 1, 2, and 3 from Escherichia coli shows that glutaredoxin 2 is the primary hydrogen donor to ArsC-catalyzed arsenate reduction.
   J. Biol. Chem. 274 : 36039-36042 (1999). [PMID: 10593884]
9. Mukhopadhyay, R., Rosen, B. P.
   Arsenate reductases in prokaryotes and eukaryotes.
   Environ. Health Perspect. 110 Suppl 5 : 745-748 (2002). [PMID: 12426124]
10. Messens, J., Silver, S.
    Arsenate reduction: thiol cascade chemistry with convergent evolution.
    J. Mol. Biol. 362 : 1-17 (2006). [PMID: 16905151]

[EC 1.20.4.1 created 2000 as EC 1.97.1.5, transferred 2001 to EC 1.20.4.1, modified 2015, modified 2019, modified 2020]