Arsenite oxidase in complex with antimonite and arsenite oxyanions: Insights into the catalytic mechanism

• Published in: The Journal of biological chemistry Vol. 299; no. 8; p. 105036
• Main Authors: Engrola, Filipa, Correia, Márcia A.S., Watson, Cameron, Romão, Carlos C., Veiros, Luis F., Romão, Maria João, Santos-Silva, Teresa, Santini, Joanne M.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2023; American Society for Biochemistry and Molecular Biology
• Subjects: antimony; arsenic; arsenite oxidase; DFT calculations; enzyme mechanism; JBC Communication; molybdenum enzyme; X-ray crystallography; X-ray crystallography; arsenite oxidase; molybdenum enzyme; antimony; DFT; SASA; MGD; enzyme mechanism; arsenic; DFT calculations
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/j.jbc.2023.105036

Arsenic contamination of groundwater is among one of the biggest health threats affecting millions of people in the world. There is an urgent need for efficient arsenic biosensors where the use of arsenic metabolizing enzymes can be explored. In this work, we have solved the crystal structures of four complexes of arsenite oxidase (Aio) obtained in complex with arsenic and antimony oxyanions and the structures determined correspond to intermediate states of the enzymatic mechanism. These structural data were complemented with density-functional theory calculations providing a unique view of the molybdenum active site at different time points that, together with mutagenesis data, enabled to clarify the enzymatic mechanism and the molecular determinants for the oxidation of As(III) to the less toxic As(V) species.