Dihydroflavin-driven Adenosylation of 4-Coordinate Co(II) Corrinoids ARE COBALAMIN REDUCTASES ENZYMES OR ELECTRON TRANSFER PROTEINS?

作者：Mera Paola E; Escalante Semerena Jorge C^*

来源：Journal of Biological Chemistry, 2010, 285(5): 2911.

DOI：10.1074/jbc.M109.059485

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 mu M). 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.

• 出版日期2010-1-29