GSBS Student Publications


Crystal structure of deoxy-human hemoglobin beta6 Glu --> Trp. Implications for the structure and formation of the sickle cell fiber

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology; Program in Molecular Medicine



Document Type


Medical Subject Headings

Amino Acid Substitution; Crystallography, X-Ray; Glutamic Acid; Hemoglobin, Sickle; Hemoglobins; Humans; Models, Molecular; Molecular Sequence Data; Protein Conformation; Tryptophan


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.

Rights and Permissions

Citation: J Biol Chem. 1998 Dec 4;273(49):32690-6.

Related Resources

Link to article in PubMed

Journal Title

The Journal of biological chemistry

PubMed ID