The crotonases comprise a widely-distributed enzyme superfamily that has multiple roles in both primary and secondary metabolism. Many crotonases employ oxyanion hole-mediated stabilisation of intermediates to catalyse reaction of coenzyme A (CoA) thioester substrates (e.g., malonyl-CoA, α,β-unsaturated CoA esters) with both nucleophiles and, in the case of enolate intermediates, with varied electrophiles. Reactions of crotonases that proceed via a stabilized oxyanion intermediate include the hydrolysis of substrates including proteins, as well as hydration, isomerization, nucleophilic aromatic substitution, Claisen-type reactions, and cofactor-independent oxidation reactions. The crotonases have a conserved fold formed from a central β-sheet core surrounded by α-helices, which typically oligomerize to form a trimer, or dimer of trimers. The presence of a common structural platform and a mechanism involving intermediates with diverse reactivity implies that the crotonases have considerable potential for biocatalysis and synthetic biology, as supported by pioneering protein engineering studies on them. In this Perspective, we give an overview of crotonase diversity and structural biology, then illustrate the scope of crotonase catalysis and potential for biocatalysis.
قسم البحث
مجلة البحث
ACS Catalysis
الناشر
American Chemical Society
تصنيف البحث
1
عدد البحث
10.1021/acscatal.7b01699
موقع البحث
http://pubs.acs.org/doi/abs/10.1021/acscatal.7b01699
سنة البحث
2017
المشارك في البحث
ملخص البحث