Enhancement of Pharmaceutical Urate Oxidase Thermostability by Rational Design of De Novo Disulfide Bridge.

ABSTRACT:

Background and purpose

As a therapeutic enzyme, urate oxidase is utilized in the reduction of uric acid in various conditions such as gout or tumor syndrome lysis. However, even bearing kinetical advantage over other counterparts, it suffers from structural instability most likely due to its subcellular and fungal origin.

Objectives

In this research, by using rational design and introduction of de novo disulfide bridge in urate oxidase structure, we designed and created a thermostable urate oxidase for the first time.

Materials and methods

Utilizing site-directed mutagenesis and only with one point mutation we constructed two separate mutants: Ala6Cys and Ser282Cys which covalently linked subunits of enzyme each other. Single mutation to cysteine created three

SUBMITTER: Rezaeian Marjani L 

PROVIDER: S-EPMC8035418 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature