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Dihydroflavin-driven adenosylation of 4-coordinate Co(II) corrinoids: are cobalamin reductases enzymes or electron transfer proteins?

ABSTRACT: The identity of the source of the biological reductant needed to convert cobalamin to its biologically active form adenosylcobalamin has remained elusive. Here we show that free or protein-bound dihydroflavins can serve as the reductant of Co(2+)Cbl bound in the active site of PduO-type ATP-dependent corrinoid adenosyltransferase enzymes. Free dihydroflavins (dihydroriboflavin, FMNH(2), and FADH(2)) effectively drove the adenosylation of Co(2+)Cbl by the human and bacterial PduO-type enzymes at very low concentrations (1 microm). These data show that adenosyltransferase enzymes lower the thermodynamic barrier of the Co(2+) --> Co(+) reduction needed for the formation of the unique organometalic Co-C bond of adenosylcobalamin. Collectively, our in vivo and in vitro data suggest that cobalamin reductases identified thus far are most likely electron transfer proteins, not enzymes.

SUBMITTER: Mera PE

PROVIDER: S-EPMC2823439 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Dihydroflavin-driven adenosylation of 4-coordinate Co(II) corrinoids: are cobalamin reductases enzymes or electron transfer proteins?

Mera Paola E PE Escalante-Semerena Jorge C JC

The Journal of biological chemistry 20091121 5

The identity of the source of the biological reductant needed to convert cobalamin to its biologically active form adenosylcobalamin has remained elusive. Here we show that free or protein-bound dihydroflavins can serve as the reductant of Co(2+)Cbl bound in the active site of PduO-type ATP-dependent corrinoid adenosyltransferase enzymes. Free dihydroflavins (dihydroriboflavin, FMNH(2), and FADH(2)) effectively drove the adenosylation of Co(2+)Cbl by the human and bacterial PduO-type enzymes at ...[more]

PMID: 19933577

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