Catalytic control of enzymatic fluorine specificity.
Proc Natl Acad Sci U S A
; 109(48): 19667-72, 2012 Nov 27.
Article
de En
| MEDLINE
| ID: mdl-23150553
ABSTRACT
The investigation of unique chemical phenotypes has led to the discovery of enzymes with interesting behaviors that allow us to explore unusual function. The organofluorine-producing microbe Streptomyces cattleya has evolved a fluoroacetyl-CoA thioesterase (FlK) that demonstrates a surprisingly high level of discrimination for a single fluorine substituent on its substrate compared with the cellularly abundant hydrogen analog, acetyl-CoA. In this report, we show that the high selectivity of FlK is achieved through catalysis rather than molecular recognition, where deprotonation at the C(α) position to form a putative ketene intermediate only occurs on the fluorinated substrate, thereby accelerating the rate of hydrolysis 10(4)-fold compared with the nonfluorinated congener. These studies provide insight into mechanisms of catalytic selectivity in a native system where the existence of two reaction pathways determines substrate rather than product selection.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Fluor
Langue:
En
Journal:
Proc Natl Acad Sci U S A
Année:
2012
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique