The research in the Bureik group encompasses two primary areas:

1) The study of human drug metabolizing enzymes and their use for organic synthesis.

A major goal in this project involves systematic testing of all variants of drug metabolizing cytochrome P450 enzymes (CYPs or P450s) and UDP glycosyltransferases (UGTs) identified in Chinese patients. This is expected to aid doctors in choosing the correct dosage for patients.

2) Investigation of human CYP4Z1 and exploitation of its activity for the treatment of breast cancer.

In this project, we have successfully identified CYP4Z1 to catalyze fatty acid in-chain hydroxylase and also ether cleavage. A primary aim is to search for compounds that can act as CYP4Z1-activated prodrugs and have potential for treatment of breast cancer.

Recently published work:

In cooperation with the group of Prof. Gerhard Wolber (Free University Berlin, Germany) we recently published a homology model of a UGT1A5 variant (UGT1A5*8) which shows that the cofactor UDP-GA is placed in a much more favorable geometry in UGT1A5*8 as compared to the wild-type, thus explaining its increased catalytical activity (Yang et al., 2018):

(A) Structural homology model for UGT1A5*8 with bound cofactor Uridine-diphosphoglucoronic acid (UDP-GA). The secondary structure ribbon is shown in grey. Helix Q is highlighted in blue. The cofactor (colored turquois) is situated in the catalytic cleft between the N-terminal (left) and C-terminal (right) domains. (B) Superposition of C-terminal domains of the UGT2B7 crystal structure (yellow) and UGT1A5*8 homology model (grey) with a root-mean square root of 2. 1 Å. (C) Cofactor protein interaction diagram for UGT1A5 and UDP-GA. The glucuronic acid moiety of UDP-GA is hold in place by electrostatic interaction with Arg174 and hydrogen bonding to Ser376 and Asp397. The uridine-diphosphate moiety forms hydrogen bonds to Ser307, Leu308, His373, His377 and Gly378. Blue double-headed arrow represents electrostatic interaction. Red arrows represent hydrogen bond acceptance and green arrow hydrogen bond donation.