Hemoglobin subunit beta (HBB) Cys93 thiol (HBB Cys93)

Hemoglobin subunit beta (HBB) Cys93 thiol is a highly conserved cysteine residue located at position 93 of the human beta-globin chain (UniProt P68871). This residue is unique among mammalian hemoglobins for its high reactivity and its role as a primary site for S-nitrosylation, forming S-nitrosohemoglobin (SNO-Hb) (Stamler et al., Science 1997). By forming SNO-Hb, this thiol group enables hemoglobin to function as a carrier for nitric oxide (NO), facilitating its transport from the lungs to the peripheral tissues (Jia et al., Nature 1996). The release of NO from this site is oxygen-dependent, occurring primarily during the transition from the R-state to the T-state in hypoxic environments to promote vasodilation (Singel & Stamler, Annual Review of Physiology 2005). In diseases such as sickle cell anemia and pulmonary hypertension, the dysregulation of S-nitrosylation at Cysβ93 contributes to impaired blood flow and tissue ischemia (Gladwin et al., Nature Medicine 2003). Therapeutic interventions targeting this thiol aim to restore NO homeostasis or modulate the allosteric properties of hemoglobin to improve oxygen delivery. Additionally, the Cysβ93 thiol is a target for various electrophilic drugs and environmental toxins that can alter hemoglobin's structural integrity and function. Its proximity to the heme iron and the C-terminal end of the beta chain makes it a critical sensor for the protein's quaternary state.

Other names

Cys-beta93Cysteine 93 of the beta-globin chainHemoglobin beta chain Cys93Cys93 thiol

The Cysβ93 thiol undergoes reversible S-nitrosylation to form S-nitrosohemoglobin, which acts as a reservoir and transporter for nitric oxide, releasing it in response to low oxygen tension to induce vasodilation.