ArticleProceedings of the National Academy of Sciences of the United States of America2016
Unique coupling of mono- and dioxygenase chemistries in a single active site promotes heme degradation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 44 citations in OpenAlex.
- Heme in Bacterial Pathogenesis and as an Antimicrobial Target.Chemical reviews · 2025Review
- Stabilization of the Ferryl═Oxoheme Form ofJournal of the American Chemical Society · 2025Article
- Heme-copper and Heme OJournal of inorganic biochemistry · 2023Review
- Second-sphere tuning of analogues for the ferric-hydroperoxoheme form of Mycobacterium tuberculosis MhuD.Journal of inorganic biochemistry · 2023Article
- Metabolomic analysis of Mycobacterium tuberculosis reveals metabolic profiles for identification of drug-resistant tuberculosis.Scientific reports · 2023Article
- Ruffling is essential for Staphylococcus aureus IsdG-catalyzed degradation of heme to staphylobilin.Journal of inorganic biochemistry · 2022Article
- Structure-function characterization of the mono- and diheme forms of MhuD, a noncanonical heme oxygenase from Mycobacterium tuberculosis.The Journal of biological chemistry · 2022Article
- A Dynamic Substrate is Required for MhuD-Catalyzed Degradation of Heme to Mycobilin.Biochemistry · 2021Article
- Heme-FeJournal of the American Chemical Society · 2020Article
- Structure of aBiochemistry · 2019Article
- Spectroscopic Evidence for Electronic Control of Heme Hydroxylation by IsdG.Inorganic chemistry · 2019Article
- Heme catabolism in the causative agent of anthrax.Molecular microbiology · 2019Article
- A Single Mutation in the Mycobacterium tuberculosis Heme-Degrading Protein, MhuD, Results in Different Products.Biochemistry · 2019Article
- Iron Acquisition in Mycobacterium tuberculosis.Chemical reviews · 2019Review
- Synthetic Fe/Cu Complexes: Toward Understanding Heme-Copper Oxidase Structure and Function.Chemical reviews · 2018Review
- The affinity of MhuD for heme is consistent with a heme degrading function in vivo.Metallomics : integrated biometal science · 2018Article
- Hydrogen sulfide bypasses the rate-limiting oxygen activation of heme oxygenase.The Journal of biological chemistry · 2018Article
- Formation and Cleavage of C-C Bonds by Enzymatic Oxidation-Reduction Reactions.Chemical reviews · 2018Review
- Reaction intermediates in the heme degradation reaction by HutZ from Vibrio cholerae.Dalton transactions (Cambridge, England : 2003) · 2017Article
- Reactions of Ferrous Coproheme Decarboxylase (HemQ) with OBiochemistry · 2017Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Bacterial pathogens must acquire host iron for survival and colonization. Because free iron is restricted in the host, numerous pathogens have evolved to overcome this limitation by using a family of monooxygenases that mediate the oxidative cleavage of heme into biliverdin, carbon monoxide, and iron. However, the etiological agent of tuberculosis, Mycobacterium tuberculosis, accomplishes this task without generating carbon monoxide, which potentially induces its latent state. Here we show that this unusual heme degradation reaction proceeds through sequential mono- and dioxygenation events within the single active center of MhuD, a mechanism unparalleled in enzyme catalysis. A key intermediate of the MhuD reaction is found to be meso-hydroxyheme, which reacts with O2 at an unusual position to completely suppress its monooxygenation but to allow ring cleavage through dioxygenation. This mechanistic change, possibly due to heavy steric deformation of hydroxyheme, rationally explains the unique heme catabolites of MhuD. Coexistence of mechanistically distinct functions is a previously unidentified strategy to expand the physiological outcome of enzymes, and may be applied to engineer unique biocatalysts.
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