IntEnz

EC 2.5.1.17 - Corrinoid adenosyltransferase

IntEnz Enzyme Nomenclature
EC 2.5.1.17

Names

Reactions

• (1) 2 ATP + 2 cob(2)alamin + a reduced flavoprotein = 2 triphosphate + 2 adenosylcob(3)alamin + an oxidized flavoprotein
•   (1a) 2 cob(2)alamin + 2 corrinoid adenosyltransferase = 2 corrinoid adenosyltransferase-cob(2)alamin
•   (1b) a reduced flavoprotein + 2 corrinoid adenosyltransferase-cob(2)alamin = an oxidized flavoprotein + 2 corrinoid adenosyltransferase-cob(1)alamin (spontaneous)
•   (1c) 2 ATP + 2 corrinoid adenosyltransferase-cob(1)alamin = 2 triphosphate + 2 adenosylcob(3)alamin + 2 corrinoid adenosyltransferase
• (2) 2 ATP + 2 cob(2)yrinic acid a,c-diamide + a reduced flavoprotein = 2 triphosphate + 2 adenosylcob(3)yrinic acid a,c-diamide + an oxidized flavoprotein
•   (2a) 2 cob(2)yrinic acid a,c-diamide + 2 corrinoid adenosyltransferase = 2 corrinoid adenosyltransferase-cob(2)yrinic acid a,c-diamide
•   (2b) a reduced flavoprotein + 2 corrinoid adenosyltransferase-cob(2)yrinic acid a,c-diamide = an oxidized flavoprotein + 2 corrinoid adenosyltransferase-cob(1)yrinic acid a,c-diamide (spontaneous)
• (3) (2c) 2 ATP + 2 corrinoid adenosyltransferase-cob(1)yrinic acid a,c-diamide = 2 triphosphate + 2 adenosylcob(3)yrinic acid a,c-diamide + 2 corrinoid adenosyltransferase

Comments:

The corrinoid adenosylation pathway comprises three steps: (i) reduction of Co(III) to Co(II) by a one-electron transfer. This can occur non-enzymically in the presence of dihydroflavin nucleotides or reduced flavoproteins [3]. (ii) Co(II) is bound by corrinoid adenosyltransferase, resulting in displacement of the lower axial ligand by an aromatic residue. The reduction potential of the 4-coordinate Co(II) intermediate is raised by ~250 mV compared with the free compound, bringing it to within physiological range. This is followed by a second single-electron transfer from either free dihydroflavins or the reduced flavin cofactor of flavoproteins, resulting in reduction to Co(I) [7]. (iii) the Co(I) conducts a nucleophilic attack on the adenosyl moiety of ATP, resulting in transfer of the deoxyadenosyl group and oxidation of the cobalt atom to Co(III) state. Three types of corrinoid adenosyltransferases, not related by sequence, have been described. In the anaerobic bacterium Salmonella enterica they are encoded by the cobA gene (a housekeeping enzyme involved in both adenosylcobalamin de novo biosynthesis and salvage), the pduO gene (involved in (S)-propane-1,2-diol utilization), and the eutT gene (involved in ethanolamine utilization). Since EutT hydrolyses triphosphate during catalysis, it is classified as a separate enzyme. The mammalian enzyme belongs to the PduO type. The enzyme can act on other corrinoids, such as cob(II)inamide.

Links to other databases

References

1. Vitols, E., Walker, G.A. and Huennekens, F.M.
   Enzymatic conversion of vitamin B_12s to a cobamide coenzyme, α-(5,6-dimethylbenzimidazolyl)deoxyadenosylcobamide (adenosyl-B₁₂).
   J. Biol. Chem. 241 : 1455-1461 (1966). [PMID: 5946606]
2. Bauer, C.B., Fonseca, M.V., Holden, H.M., Thoden, J.B., Thompson, T.B., Escalante-Semerena, J.C. and Rayment, I.
   Three-dimensional structure of ATP:corrinoid adenosyltransferase from Salmonella typhimurium in its free state, complexed with MgATP, or complexed with hydroxycobalamin and MgATP.
   Biochemistry 40 : 361-374 (2001). [PMID: 11148030]
3. Fonseca, M. V., Escalante-Semerena, J. C.
   Reduction of Cob(III)alamin to Cob(II)alamin in Salmonella enterica serovar typhimurium LT2.
   J. Bacteriol. 182 : 4304-4309 (2000). [PMID: 10894741]
4. Fonseca, M.V. and Escalante-Semerena, J.C.
   An in vitro reducing system for the enzymic conversion of cobalamin to adenosylcobalamin.
   J. Biol. Chem. 276 : 32101-32108 (2001). [PMID: 11408479]
5. Suh, S. and Escalante-Semerena, J.C.
   Purification and initial characterization of the ATP:corrinoid adenosyltransferase encoded by the cobA gene of Salmonella typhimurium.
   J. Bacteriol. 177 : 921-925 (1995). [PMID: 7860601]
6. Mera, P. E., St Maurice, M., Rayment, I., Escalante-Semerena, J. C.
   Residue Phe112 of the human-type corrinoid adenosyltransferase (PduO) enzyme of Lactobacillus reuteri is critical to the formation of the four-coordinate Co(II) corrinoid substrate and to the activity of the enzyme.
   Biochemistry 48 : 3138-3145 (2009). [PMID: 19236001]
7. Mera, P. E., Escalante-Semerena, J. C.
   Dihydroflavin-driven adenosylation of 4-coordinate Co(II) corrinoids: are cobalamin reductases enzymes or electron transfer proteins?
   J. Biol. Chem. 285 : 2911-2917 (2010). [PMID: 19933577]

[EC 2.5.1.17 created 1972, modified 2004, modified 2018]