Blockage of the channel to heme by the E87 side chain in the GAF domain of Mycobacterium tuberculosis DosS confers the unique sensitivity of DosS to oxygen

► A channel to the heme in DosS can be blocked by E87. ► DosT has an open channel to heme due to G85. ► DosS mutants with an open channel bind oxygen when they are exposed to air. ► DosT mutant is oxidized similarly to DosS without formation of an oxy-ferrous form.