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Moraxella catarrhalis HemW is a Heme-binding Radical SAM Enzyme

Padgett, C. M.; Bollmeyer, M. M.; Boswinkle, K.; de Crecy-Lagard, V.; Britt, R. D.; Zhu, W.

2026-01-25 biochemistry
10.64898/2026.01.24.701380 bioRxiv
Show abstract

Moraxella catarrhalis is an emerging human respiratory pathogen responsible for a significant proportion of childhood otitis media and exacerbations of chronic obstructive pulmonary disease. Recent transposon sequencing analysis identified yggW (renamed as hemW), an uncharacterized gene, as essential for M. catarrhalis growth under iron-limiting conditions, mimicking host-imposed nutritional immunity. HemW is annotated as a putative radical S-adenosylmethionine (SAM) enzyme and belongs to the HemN-like subfamily, but its biochemical properties remain unclear. Here, we report on the first experimental characterizations of McHemW. Our bioinformatic analysis confirmed its evolutionary relationship with the putative heme-binding radical SAM enzyme EcHemW in Escherichia coli. Using biochemical and spectroscopic approaches, we demonstrate that McHemW contains a catalytically active [4Fe-4S] cluster and binds heme in vitro. These findings support a functional role for McHemW as a putative heme chaperone, highlighting it as a potential target for disrupting iron metabolism in this clinically important pathogen.

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