Structure and Functional Differences of Cysteine and 3-Mercaptopropionate Dioxygenases: A Computational Study.

Thiol dioxygenases are important enzymes for human health; they are involved in the detoxification and catabolism of toxic thiol-containing natural products such as cysteine. As such, these enzymes have relevance to the development of Alzheimer's and Parkinson's diseases in the brain. Recent crystal structure coordinates of cysteine and 3-mercaptopropionate dioxygenase (CDO and MDO) showed major differences in the second-coordination spheres of the two enzymes. To understand the difference in activity between these two analogous enzymes, we created large, active-site cluster models. We show that CDO and MDO have different iron(III)-superoxo-bound structures due to differences in ligand coordination. Furthermore, our studies show that the differences in the second-coordination sphere and particularly the position of a positively charged Arg residue results in changes in substrate positioning, mobility and enzymatic turnover. Furthermore, the substrate scope of MDO is explored with cysteinate and 2-mercaptosuccinic acid and their reactivity is predicted. © 2021 Wiley-VCH GmbH.

Citation

C-C George Yeh, Christos Pierides, Guy N L Jameson, Sam P de Visser. Structure and Functional Differences of Cysteine and 3-Mercaptopropionate Dioxygenases: A Computational Study. Chemistry (Weinheim an der Bergstrasse, Germany). 2021 Oct 01;27(55):13793-13806

Mesh Tags

Substances

PMID: 34310770

search → result