Cardiff University | Prifysgol Caerdydd ORCA
Online Research @ Cardiff 
WelshClear Cookie - decide language by browser settings

Synthetic Efficiency in Enzyme Mechanisms Involving Carbocations:  Aristolochene Synthase

Allemann, Rudolf Konrad ORCID: https://orcid.org/0000-0002-1323-8830, Young, Neil James, Ma, Shuhua, Truhlar, Donald G. and Gao, Jiali 2007. Synthetic Efficiency in Enzyme Mechanisms Involving Carbocations:  Aristolochene Synthase. Journal of the American Chemical Society 129 (43) , pp. 13008-13013. 10.1021/ja0722067

Full text not available from this repository.

Abstract

An intramolecular proton-transfer mechanism has been proposed for the carbocationic cyclization of farnesyl pyrophosphate (FPP) to (+)-aristolochene catalyzed by aristolochene synthase. This novel mechanism, which is based on results obtained by high-level ab initio molecular orbital and density functional theory calculations, differs from the previous proposal in the key step of carbocation propagation prior to the formation of the bicyclic carbon skeleton. Previously, germacrene A was proposed to be generated as an intermediate by deprotonation of germacryl cation followed by reprotonation of the C6−C7 double bond to yield eudesmane cation. In the mechanism proposed here the direct intramolecular proton transfer has a computed barrier of about 22 kcal/mol, which is further lowered to 16−20 kcal/mol by aristolochene synthase. An alternative pathway is also possible through a proton shuttle via a pyrophosphate-bound water molecule. The mechanism proposed here is consistent with the observation that germacrene A is not a substrate of aristolochene synthase. Furthermore, the modeled substrate−enzyme complex suggests that Trp 334 and Phe 178 play key roles in positioning the substrate in the reactive orientation in the binding pocket. This is consistent with experimental findings that mutations of either residue lead to pronounced generation of aborted cyclization products.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Cardiff Catalysis Institute (CCI)
Chemistry
Subjects: Q Science > QD Chemistry
Publisher: American Chemical Society
ISSN: 0002-7863
Last Modified: 18 Oct 2022 14:02
URI: https://orca.cardiff.ac.uk/id/eprint/16236

Citation Data

Cited 48 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item Edit Item