5UCU

STRUCTURAL AND MECHANISTIC INSIGHTS INTO HEMOGLOBIN-CATALYZED HYDROGEN SULFIDE OXIDATION AND THE FATE OF POLYSULFIDE PRODUCTS

Summary for 5UCU

• Entry DOI: 10.2210/pdb5ucu/pdb
• Descriptor: Hemoglobin subunit alpha, Hemoglobin subunit beta, PROTOPORPHYRIN IX CONTAINING FE, ... (5 entities in total)
• Functional Keywords: mechanism of hemoglobin catalyzed h2s oxidation, oxygen transport
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 2
• Total formula weight: 32375.77

Authors

Vitvitsky, V.,Yadav, P.K.,An, S.,Seravalli, J.,Cho, U.-S.,Banerjee, R. (deposition date: 2016-12-22, release date: 2017-03-01, Last modification date: 2023-10-04)

Primary citation

Vitvitsky, V.,Yadav, P.K.,An, S.,Seravalli, J.,Cho, U.S.,Banerjee, R.
Structural and Mechanistic Insights into Hemoglobin-catalyzed Hydrogen Sulfide Oxidation and the Fate of Polysulfide Products.
J. Biol. Chem., 292:5584-5592, 2017

PubMed Abstract: Hydrogen sulfide is a cardioprotective signaling molecule but is toxic at elevated concentrations. Red blood cells can synthesize HS but, lacking organelles, cannot dispose of HS via the mitochondrial sulfide oxidation pathway. We have recently shown that at high sulfide concentrations, ferric hemoglobin oxidizes HS to a mixture of thiosulfate and iron-bound polysulfides in which the latter species predominates. Here, we report the crystal structure of human hemoglobin containing low spin ferric sulfide, the first intermediate in heme-catalyzed sulfide oxidation. The structure provides molecular insights into why sulfide is susceptible to oxidation in human hemoglobin but is stabilized against it in HbI, a specialized sulfide-carrying hemoglobin from a mollusk adapted to life in a sulfide-rich environment. We have also captured a second sulfide bound at a postulated ligand entry/exit site in the α-subunit of hemoglobin, which, to the best of our knowledge, represents the first direct evidence for this site being used to access the heme iron. Hydrodisulfide, a postulated intermediate at the junction between thiosulfate and polysulfide formation, coordinates ferric hemoglobin and, in the presence of air, generated thiosulfate. At low sulfide/heme iron ratios, the product distribution between thiosulfate and iron-bound polysulfides was approximately equal. The iron-bound polysulfides were unstable at physiological glutathione concentrations and were reduced with concomitant formation of glutathione persulfide, glutathione disulfide, and HS. Hence, although polysulfides are unlikely to be stable in the reducing intracellular milieu, glutathione persulfide could serve as a persulfide donor for protein persulfidation, a posttranslational modification by which HS is postulated to signal.

PubMed: 28213526
DOI: 10.1074/jbc.M117.774943

Experimental method

X-RAY DIFFRACTION (1.797 Å)