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Rationalisation of the substrate concentration dependent diastereoselectivity of a Saccharomyces cerevisiae short-chain dehydrogenase

Carlquist, Magnus LU ; Johanson, Ted LU and Gorwa-Grauslund, Marie-Francoise LU (2007) In Tetrahedron: Asymmetry 18(21). p.2554-2556
Abstract
The diastereoselectivity of the carbonyl reduction of bicyclo[2.2.2]octane-2,6-dione, catalysed by the purified yeast cytosolic short-chain dehydrogenase Ymr226cp, was shown to be substrate concentration dependent. The changing selectivity was attributed to two distinct binding configurations of the substrate in the active site, each yielding a distinct hydroxy ketone diastereomer. By applying individual KM and Vmax values for each binding configuration, the concentration dependence could be modelled with Michaelis–Menten kinetics and the apparent KM and Vmax values for the generation of each diastereomer determined. This is to the best of our knowledge the first rationalisation of a substrate dependent stereoselectivity for a pro-chiral... (More)
The diastereoselectivity of the carbonyl reduction of bicyclo[2.2.2]octane-2,6-dione, catalysed by the purified yeast cytosolic short-chain dehydrogenase Ymr226cp, was shown to be substrate concentration dependent. The changing selectivity was attributed to two distinct binding configurations of the substrate in the active site, each yielding a distinct hydroxy ketone diastereomer. By applying individual KM and Vmax values for each binding configuration, the concentration dependence could be modelled with Michaelis–Menten kinetics and the apparent KM and Vmax values for the generation of each diastereomer determined. This is to the best of our knowledge the first rationalisation of a substrate dependent stereoselectivity for a pro-chiral substrate with an isolated enzyme. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Tetrahedron: Asymmetry
volume
18
issue
21
pages
2554 - 2556
publisher
Elsevier
external identifiers
  • wos:000251621600010
  • scopus:36148950068
ISSN
0957-4166
DOI
10.1016/j.tetasy.2007.10.020
language
English
LU publication?
yes
id
8c40dd5f-0e45-4cc2-9d08-e602b6a84833 (old id 935727)
date added to LUP
2008-01-17 14:57:42
date last changed
2017-01-01 07:15:53
@article{8c40dd5f-0e45-4cc2-9d08-e602b6a84833,
  abstract     = {The diastereoselectivity of the carbonyl reduction of bicyclo[2.2.2]octane-2,6-dione, catalysed by the purified yeast cytosolic short-chain dehydrogenase Ymr226cp, was shown to be substrate concentration dependent. The changing selectivity was attributed to two distinct binding configurations of the substrate in the active site, each yielding a distinct hydroxy ketone diastereomer. By applying individual KM and Vmax values for each binding configuration, the concentration dependence could be modelled with Michaelis–Menten kinetics and the apparent KM and Vmax values for the generation of each diastereomer determined. This is to the best of our knowledge the first rationalisation of a substrate dependent stereoselectivity for a pro-chiral substrate with an isolated enzyme.},
  author       = {Carlquist, Magnus and Johanson, Ted and Gorwa-Grauslund, Marie-Francoise},
  issn         = {0957-4166},
  language     = {eng},
  number       = {21},
  pages        = {2554--2556},
  publisher    = {Elsevier},
  series       = {Tetrahedron: Asymmetry},
  title        = {Rationalisation of the substrate concentration dependent diastereoselectivity of a Saccharomyces cerevisiae short-chain dehydrogenase},
  url          = {http://dx.doi.org/10.1016/j.tetasy.2007.10.020},
  volume       = {18},
  year         = {2007},
}