Heme sensors are essential for diverse physiological functions in all forms of life. From NO sensing human soluble guanylate cyclase to O2 sensing bacterial H-NOX proteins, heme sensors are utilized by various species to sense the redox stimuli in their microenvironment and adapt to it. How heme sensors differentiate between similar redox stimuli such as O2, NO, and CO is not understood. Moreover, mechanisms to rewire redox stimuli specificity of heme sensors are not known. In the ACS talk, I will discuss our lab's latest research on decoding and rewiring redox sensing and signaling specificity of heme sensors. By rationally modulating the tertiary coordination sphere of M. tuberculosis's heme sensor, we have transformed it from an NO sensor to an O2 sensor. Our results show that the hydrogen bonding and tertiary coordination sphere of heme plays an important role in controlling redox stimuli specificity and sensing mechanisms of heme proteins. Our work opens a new direction towards reprograming cellular redox biology, re-instating redox homeostasis, and curing redox-related diseases such as cancer and neurodegeneration.

Tertiary coordination sphere of heme proteins control their redox sensing emchanisms

ACS Spring 2022

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