Crystal structure of deoxy-human hemoglobin beta6 Glu --> Trp. Implications for the structure and formation of the sickle cell fiber
Department of Biochemistry and Molecular Pharmacology; Program in Molecular Medicine
Life Sciences | Medicine and Health Sciences
An atomic-level understanding of the interactions between hemoglobin molecules that contribute to the formation of pathological fibers in sickle cell disease remains elusive. By exploring crystal structures of mutant hemoglobins with altered polymerization properties, insight can be gained into sickle cell hemoglobin (HbS) polymerization. We present here the 2.0-A resolution deoxy crystal structure of human hemoglobin mutated to tryptophan at the beta6 position, the site of the glutamate --> valine mutation in HbS. Unlike leucine and isoleucine, which promote polymerization relative to HbS, tryptophan inhibits polymerization. Our results provide explanations for the altered polymerization properties and reveal a fundamentally different double strand that may provide a model for interactions within a fiber and/or interactions leading to heterogeneous nucleation.
J Biol Chem. 1998 Dec 4;273(49):32690-6.
The Journal of biological chemistry
Harrington, Daniel John; Adachi, Kengo; and Royer, William E., "Crystal structure of deoxy-human hemoglobin beta6 Glu --> Trp. Implications for the structure and formation of the sickle cell fiber" (1998). GSBS Student Publications. 472.