Prochiral sulfide probes for the active-site topography of rabbit flavin-containing monooxygenase 2 (FMO2)

✍ Scribed by Michael B. Fisher; Allan E. Rettie

• Book ID: 104361062
• Publisher: Elsevier Science
• Year: 1997
• Tongue: English
• Weight: 385 KB
• Volume: 8
• Category: Article
• ISSN: 0957-4166
• DOI: 10.1016/s0957-4166(97)00033-5

✦ Synopsis

Mammalian flavin-containing monooxygenases are known to oxygenate prochiral sulfides often with a high degree of stereoselectivity. In the present study we used two homologous series of n-alkyl aryl sulfides, Ar-S-(CH2)nH, (where Ar=p-tolyl or 2-naphthyl and n=l-7), to probe the active site topography of rabbit lung FMO2. Purified FMO2 was incubated with each member of the the p-tolyl or 2-naphthyl series and the stereochemistry of NADPH-dependent enzymatic sulfoxidation was determined. Within the p-tolyl series each member was a substrate for FMO2 and a complete reversal of stereospecificity was observed as the n-alkyl chain length increased from the methyl homolog [99% (R)] to the heptyl derivative [97% (S)]. In contrast, FMO2 generated metabolites from only the short-chain 2-naphthyl sulfides and in each case only the (R)sulfoxides were formed. The data are discussed in terms of an active-site model for FMO2 which contains two binding determinants.