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

Autor:	Guy N. L. Jameson, Sam P. de Visser, C.-C. George Yeh, Christos Pierides
Rok vydání:	2021
Předmět:	chemistry.chemical_classification biology Catabolism Chemistry Stereochemistry Ligand Organic Chemistry Cysteine Dioxygenase Cysteine dioxygenase Substrate (chemistry) General Chemistry Ferric Compounds Catalysis Dioxygenases Enzyme Dioxygenase Catalytic Domain Thiol biology.protein Humans Cysteine
Zdroj:	University of Manchester-PURE
ISSN:	1521-3765 0947-6539
DOI:	10.1002/chem.202101878
Popis:	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.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8fff33222a588dd5faa81fe42cbc8de3 https://doi.org/10.1002/chem.202101878 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
Nepřihlášeným uživatelům se plný text nezobrazuje	K zobrazení výsledku je třeba se přihlásit.