Journal
BIOCHEMISTRY
Volume 49, Issue 6, Pages 1176-1182Publisher
AMER CHEMICAL SOC
DOI: 10.1021/bi901772w
Keywords
-
Categories
Funding
- National Institutes of Health [GM40392]
Ask authors/readers for more resources
Isopenicillin N synthase (IPNS) can have both oxidase and oxygenase activity depending on the substrate. For the native substrate, ACV, oxidase activity exists; however, for the substrate analogue ACOV, which lacks ail amide nitrogen, IPNS exhibits oxygenase activity. The potential energy surfaces for the O-O bond elongation and cleavage Were calculated for three different reactions: homolytic cleavage via traditional Fenton chemistry, heterolytic cleavage, and nucleophilic attack. These surfaces show that the hydroperoxide ferrous intermediate, formed by O(2)-activated H atom abstraction from the substrate, can exploit different reaction pathways and that interactions with the substrate govern the pathway. The hydrogen bonds from hydroperoxide to the amide nitrogen of ACV polarize the sigma* orbital of the peroxide toward the proximal oxygen, facilitating heterolytic cleavage. For the substrate analogue ACOV, this hydrogen bond is no longer present, leading to nucleophilic attack on the Substrate intermediate C-S bond. After cleavage of the hydroperoxide, the two reaction pathways proceed with minimal barriers, resulting in the closure of the beta-lactam ring for the oxidase activity (ACV) or formation of the thiocarboxylate for oxygenase activity (ACOV).
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available