8CZP
2.25 angstrom resolution crystal structure of as-isolated KatG from Mycobacterium tuberculosis with an MYW cofactor
Summary for 8CZP
Entry DOI | 10.2210/pdb8czp/pdb |
Descriptor | Catalase-peroxidase, PROTOPORPHYRIN IX CONTAINING FE, ACETATE ION, ... (4 entities in total) |
Functional Keywords | met-tyr-trp cofactor, heme-dependent enzyme, oxidoreductase |
Biological source | Mycobacterium tuberculosis |
Total number of polymer chains | 2 |
Total formula weight | 162854.28 |
Authors | |
Primary citation | Li, J.,Duan, R.,Traore, E.S.,Nguyen, R.C.,Davis, I.,Griffth, W.P.,Goodwin, D.C.,Jarzecki, A.A.,Liu, A. Indole-N-Linked Hydroperoxyl Adduct of Protein-Derived Cofactor Modulating Catalase-Peroxidase Functions. Angew.Chem.Int.Ed.Engl., :e202407018-e202407018, 2024 Cited by PubMed Abstract: 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. PubMed: 39300819DOI: 10.1002/anie.202407018 PDB entries with the same primary citation |
Experimental method | X-RAY DIFFRACTION (2.25 Å) |
Structure validation
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