The high resolution crystal structure of deoxyhemoglobin S
Biochemistry & Molecular Pharmacology
Department of Biochemistry and Molecular Pharmacology
Medical Subject Headings
*Anemia, Sickle Cell; Computer Simulation; Hemoglobin, Sickle; Humans; Models, Molecular; Molecular Sequence Data; Movement; Polymers; Protein Conformation
Life Sciences | Medicine and Health Sciences
We have refined the crystal structure of deoxyhemoglobin S (beta Glu6-->Val) at 2.05 A resolution to an R-factor of 16.5% (free R=21. 5%) using crystals isomorphous to those originally grown by Wishner and Love. A predominant feature of this crystal form is a double strand of hemoglobin tetramers that has been shown by a variety of techniques to be the fundamental building block of the intracellular sickle cell fiber. The double strand is stabilized by lateral contacts involving the mutant valine interacting with a pocket between the E and F helices on another tetramer. The new structure reveals some marked differences from the previously refined 3.0 A resolution structure, including several residues in the lateral contact which have shifted by as much as 3.5 A. The lateral contact includes, in addition to the hydrophobic interactions involving the mutant valine, hydrophilic interactions and bridging water molecules at the periphery of the contact. This structure provides further insights into hemoglobin polymerization and may be useful for the structure-based design of therapeutic agents to treat sickle cell disease.
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Citation: J Mol Biol. 1997 Sep 26;272(3):398-407. Link to article on publisher's site
Journal of molecular biology
Harrington, Daniel John; Adachi, Kengo; and Royer, William E., "The high resolution crystal structure of deoxyhemoglobin S" (1997). GSBS Student Publications. 471.