Structure-function characterization of the mono- and diheme forms of MhuD, a noncanonical heme oxygenase from Mycobacterium tuberculosis.

ABSTRACT: MhuD is a noncanonical heme oxygenase (HO) from Mycobacterium tuberculosis (Mtb) that catalyzes unique heme degradation chemistry distinct from canonical HOs, generating mycobilin products without releasing carbon monoxide. Its crucial role in the Mtb heme uptake pathway has identified MhuD as an auspicious drug target. MhuD is capable of binding either one or two hemes within a single active site, but only the monoheme form was previously reported to be enzymatically active. Here we employed resonance Raman (rR) spectroscopy to examine several factors proposed to impact the reactivity of mono- and diheme MhuD, including heme ruffling, heme pocket hydrophobicity, and amino acid-heme interactions. We determined that the distal heme in the diheme MhuD active site has negligible effects on bo

SUBMITTER: Snyder SN 

PROVIDER: S-EPMC8801480 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature