Monomer-dimer structural comparison in quinol-dependent nitric oxide reductase reveals a functional basis for superior enzymatic activity in the dimer

Abstract The leading cause of bacterial meningitis, Neisseria meningitidis, deploys a quinol-dependent nitric oxide reductase (NmqNOR), belonging to the heme-copper oxidase superfamily. By detoxifying NO, an antimicrobial gas produced by host’s immune system, qNOR enables pathogen survival within hosts. Here, we determined cryoEM structures of the less active monomer and highly active dimer of NmqNOR at resolutions of 2.25 and 1.89 ?, respectively, showing the structural elements responsible for effective NO reduction. Helical disorder at the dimer interface, associated with an altered conformation of the critical Glu563 near the heme/non-heme Fe active site, was observed in the monomer. These findings suggest that dimerization stabilizes the active conformation of Glu563 through the structural network between the dimerization site and the active site. Since other members of the heme-copper oxidases exhibit dimerization, the current data on qNOR helps us understand a regulatory mechanism related to the function of heme-copper oxidases upon oligomerization. TeaserCryoEM structures unveil a functional rationale for dimerization in nitric oxide detoxifying enzyme from a pathogen