On how the conformation of biliverdins influences their reduction to bilirubins: a biological and molecular modeling study

MORA ME; BARI SE; AWRUCH J; DELFINO JM

BIOORGANIC & MEDICINAL CHEMISTRY.

Año: 2003 vol. 11 p. 4661 - 4672

0968-0896

The cyclic 2,18-bridged biliverdin (2) is excreted in rat bile without reduction to the corresponding bilirubin. Conformational analysis, employing an optimized Monte Carlo method and a mixed Monte Carlo/stochastic dynamics, reveals that biliverdin IXalpha (1) and the cyclic analogue 2 adopt 'lock washer' conformations, stabilized by the presence of intramolecular hydrogen bonds between N23...H22N and, to a lesser extent, between N23...H24N. Although 2 is very similar in overall shape to 1, the former adopts a 'locked lock washer' conformation unable to undergo fluctuations, thus possibly hampering a proper recognition by biliverdin reductase.