Indole N-Linked Hydroperoxyl Adduct of Protein-Derived Cofactor Modulating Catalase-Peroxidase Functions.

Autor: Li J; Department of Chemistry, The University of Texas at San Antonio, 1 UTSA Circle, San Antonio, TX 78249, USA., Duan R; Department of Chemistry, The University of Texas at San Antonio, 1 UTSA Circle, San Antonio, TX 78249, USA., Traore ES; Department of Chemistry, The University of Texas at San Antonio, 1 UTSA Circle, San Antonio, TX 78249, USA., Nguyen RC; Department of Chemistry, The University of Texas at San Antonio, 1 UTSA Circle, San Antonio, TX 78249, USA., Davis I; Department of Chemistry, The University of Texas at San Antonio, 1 UTSA Circle, San Antonio, TX 78249, USA., Griffth WP; Department of Chemistry, The University of Texas at San Antonio, 1 UTSA Circle, San Antonio, TX 78249, USA., Goodwin DC; Department of Chemistry and Biochemistry, Auburn University, Auburn, AL 36849, USA., Jarzecki AA; Department of Chemistry and Biochemistry, Brooklyn College, New York, NY 11210, USA., Liu A; Department of Chemistry, The University of Texas at San Antonio, 1 UTSA Circle, San Antonio, TX 78249, USA.
Jazyk: angličtina
Zdroj: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2024 Dec 02; Vol. 63 (49), pp. e202407018. Date of Electronic Publication: 2024 Nov 04.
DOI: 10.1002/anie.202407018
Abstrakt: Bifunctional catalase-peroxidase (KatG) features a posttranslational methionine-tyrosine-tryptophan (MYW) crosslinked cofactor crucial for its catalase function, enabling pathogens to neutralize hydrogen peroxide during infection. We discovered the presence of indole nitrogen-linked hydroperoxyl adduct (MYW-OOH) in Mycobacterium tuberculosis KatG in the solution state under ambient conditions, suggesting its natural occurrence. By isolating predominantly MYW-OOH-containing KatG protein, we investigated the chemical stability and functional impact of MYW-OOH. We discovered that MYW-OOH inhibits catalase activity, presenting a unique temporary lock. Exposure to peroxide or increased temperature removes the hydroperoxyl adduct from the protein cofactor, converting MYW-OOH to MYW and restoring the detoxifying ability of the enzyme against hydrogen peroxide. Thus, the N-linked hydroperoxyl group is releasable. KatG with MYW-OOH represents a catalase dormant, but primed, state of the enzyme. These findings provide insight into chemical strategies targeting the bifunctional enzyme KatG in pathogens, highlighting the role of N-linked hydroperoxyl modifications in enzymatic function.
(© 2024 Wiley-VCH GmbH.)
Databáze: MEDLINE
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