L-mandelate dehydrogenase activity

نویسندگان

  • Rhona SINCLAIR
  • Graeme A. REID
  • Stephen K. CHAPMAN
چکیده

Flavocytochrome b # from Saccharomyces cereŠisiae is an lactate dehydrogenase which exhibits only barely detectable activity levels towards another 2-hydroxyacid, -mandelate. Using protein engineering methods we have altered the active site of flavocytochrome b # and successfully introduced substantial mandelate dehydrogenase activity into the enzyme. Changes to Ala-198 and Leu-230 have significant effects on the ability of the enzyme to utilize -mandelate as a substrate. The doublemutation of Ala-198!Gly and Leu-230!Ala results in an enzyme with a k cat value (25 °C) with -mandelate of 8.5 s−", which represents an increase of greater than 400-fold over the wild-type enzyme. Perhaps more significantly, the mutant enzyme has a catalytic efficiency (as judged by k cat }K m values) that is 6-fold higher with -mandelate than it is with -lactate. Closer examination of the X-ray structure of S. cereŠisiae flavocytochrome b # led us to

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تاریخ انتشار 1998