Mycobacterium lepromatosis MLPM_5000 is a potential heme chaperone protein HemW and mis-annotation of its orthologues in mycobacteria

Sharma, Mukul; Gupta, Yash; Dwivedi, Purna; Kempaiah, Prakasha; Singh, Pushpendra

doi:10.1016/j.meegid.2021.105015

Cited by 5 publications

(5 citation statements)

References 32 publications

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“…The iron-storage protein bacterioferritins potentially serve as a heme donor for HemW, which can transfer heme to a heme-depleted, catalytically inactive nitrate reductase to restore its nitrate reductase activity . How heme is bound to HemW is not clear, and molecular dynamics analysis showed that heme likely interacts with the conserved HNXXYW motif in the mycobacterial HemW . Future studies are awaited to reveal the detailed function and mechanism of HemW.…”

Section: Other Hemn-like Proteinsmentioning

confidence: 99%

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Functional Diversity of HemN-like Proteins

Cheng

Liu

Zhu

et al. 2022

ACS Bio Med Chem Au

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HemN is a radical S-adenosylmethionine (SAM) enzyme that catalyzes the anaerobic oxidative decarboxylation of coproporphyrinogen III to produce protoporphyrinogen IX, a key intermediate in heme biosynthesis. Proteins homologous to HemN (HemN-like proteins) are widespread in both prokaryotes and eukaryotes. Although these proteins are in most cases annotated as anaerobic coproporphyrinogen III oxidases (CPOs) in the public database, many of them are actually not CPOs but have diverse functions such as methyltransferases, cyclopropanases, heme chaperones, to name a few. This Perspective discusses the recent advances in the understanding of HemN-like proteins, and particular focus is placed on the diverse chemistries and functions of this growing protein family.

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Section: Other Hemn-like Proteinsmentioning

confidence: 99%

“… 90 How heme is bound to HemW is not clear, and molecular dynamics analysis showed that heme likely interacts with the conserved HNXXYW motif in the mycobacterial HemW. 91 Future studies are awaited to reveal the detailed function and mechanism of HemW.…”

Section: Other Hemn-like Proteinsmentioning

confidence: 99%

Functional Diversity of HemN-like Proteins

Cheng

Liu

Zhu

et al. 2022

ACS Bio Med Chem Au

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“…The gene hemW, previously annotated as hemN (10), was found in M. lepromatosis (MLPF_2234) but not in M. leprae. This gene likely encodes a heme chaperone that catalyzes the insertion of heme into hemoproteins for respiration (43,44). The gene and adjacent MLPF_2235 (a pseudogene) stood between syntenic blocks 19 and 20 (Table S4); in M. leprae, however, the syntenic blocks rearranged afar after divergence, during which hemW and adjacent pseudogene (together ;2 kb) were likely lost.…”

Section: Resultsmentioning

confidence: 99%

Construction and Analysis of the Complete Genome Sequence of Leprosy Agent Mycobacterium lepromatosis

et al. 2022

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Leprosy is a dreaded infection that still affects millions of people worldwide. Mycobacterium lepromatosis is a recently recognized cause in addition to the well-known Mycobacterium leprae . M. lepromatosis is likely specific for diffuse lepromatous leprosy, a severe form of the infection and endemic in Mexico. This study constructed and annotated the complete genome sequence of M. lepromatosis FJ924 and performed comparative genomic analyses with related mycobacteria.

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“…Another type of heme chaperones are the mycobacterial orthologues which were shown, by phylogenetic analysis, to form a divergent clade that includes the HemW proteins of other species such as Escherichia coli and Lactococcus lactis (Sharma et al 2021). Molecular dynamics studies showed that in mycobacteria HemW binds heme through the conserved H250NXXYW255 motif.…”

Section: Discussionmentioning

confidence: 99%

InCampylobacter jejunia new type of chaperone receives hemebfrom ferrochelatase

Beas

Videira

Karavaeva

et al. 2023

Preprint

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Intracellular heme formation and trafficking are fundamental processes in living organisms. Three biogenesis pathways are used by bacteria and archaea to produce iron protoporphyrin IX (heme b) that diverge after the formation of the common intermediate uroporphyrinogen III (uro'gen III). In this work, we identify and provide a detailed characterization of the enzymes involved in the transformation of uro'gen III into heme. We show that in this organism operates the protoporphyrin-dependent pathway (PPD pathway), in which the last reaction is the incorporation of ferrous iron into the porphyrin ring by the ferrochelatase enzyme. In general, following this final reaction, little is known about how the formed heme b reaches the target proteins. In particular, the chaperons that are thought to be required to traffic heme for incorporation into hemeproteins to avoid the cytotoxicity associated to free heme, remain largely unidentified. We identified in C. jejuni a chaperon-like protein, named CgdH2, that binds heme with a dissociation constant of 4.9 ± 1.0 μM, a binding that is impaired upon mutation of residues histidine 45 and 133. We show that C. jejuni CgdH2 establishes protein-protein interactions with ferrochelatase, which should enable for the observed transfer of heme from ferrochelatase to CgdH2. Phylogenetic analysis revealed that C. jejuni CgdH2 is evolutionarily distinct from the currently known chaperones. Therefore, CgdH2 is a novel chaperone and the first protein identified as an acceptor of the intracellularly formed heme, thus enlarging our understanding of bacterial heme homeostasis.

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Mycobacterium lepromatosis MLPM_5000 is a potential heme chaperone protein HemW and mis-annotation of its orthologues in mycobacteria

Cited by 5 publications

References 32 publications

Functional Diversity of HemN-like Proteins

Functional Diversity of HemN-like Proteins

Construction and Analysis of the Complete Genome Sequence of Leprosy Agent Mycobacterium lepromatosis

InCampylobacter jejunia new type of chaperone receives hemebfrom ferrochelatase

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