Hemoglobin Degradation Compounds Revealed

Researchers have found three breakdown intermediates of human hemoglobin that form when ubiquitous nitrite anions from soil, plants, and other sources interact with the protein. Hemoglobin plays a central role in oxygen binding and transport and nitric oxide signaling. Nitrite binding to the protein is a physiologically important process that can induce hemoglobin degradation. In some cases, the degradation leads to loss of one or more of hemoglobin’s four heme groups, and such heme losses are known to occur in malaria and other blood-borne diseases. But no structural information on hemoglobin’s nitrite-induced degradation intermediates was available. Now, research assistant professor Jun Yi and professor George B. Richter-Addo of the University of Oklahoma, Norman, and coworkers have used X-ray crystallography to structurally analyze several breakdown products (Biochemistry, DOI: 10.1021/bi2009322). One is a hemoglobin compound in which heme is displaced 4.8 Å from its normal location—the largest heme slippage observed for any heme protein—and in which nitrite is bound in an unprecedented way. The results provide structural insights into a possible pathway for nitrite-induced heme loss from human hemoglobin, the researchers note.