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COHbC and COHbS crystallize in the R2 quaternary state at neutral pH in the presence of PEG 4000.

Patskovska LN, Patskovsky YV, Almo SC, Hirsch RE
Acta Crystallogr D Biol Crystallogr 61 566-73 (2005)
Cited: 6 times
EuropePMC logo PMID: 15858266

Abstract

Human hemoglobin binds oxygen cooperatively and functions as a tetramer composed of two identical alphabeta heterodimers. While human hemoglobin is the best characterized allosteric protein, the quaternary R (oxygenated or liganded) to T (deoxygenated) structural transition remains controversial. The R2 state has been postulated to represent either an intermediate or final quaternary state elicited by ligand binding. However, the biological relevance of the R2 state has been questioned as it has not been observed crystallographically under physiological conditions. The high-resolution R2 quaternary structures of human COHbC (betaE6K) and COHbS (betaE6V) are reported at neutral pH and low ionic strength using PEG 4000 as a precipitant. Crystals of COHbC, COHbS and their mixtures are isomorphous, indicating that they share the same tertiary and quaternary structures. In contrast, oxyHbA or COHbA did not yield crystals at neutral pH under similar conditions. Solubility studies and modeling suggest that at neutral pH and low ionic strength the beta6 mutant hemoglobins crystallize (betaK6 > betaV6) as a result of more favorable lattice contacts.

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  1. Crystal structure of carbonmonoxy sickle hemoglobin in R-state conformation. Ghatge MS, Ahmed MH, Omar AS, Pagare PP, Rosef S, Kellogg GE, Abdulmalik O, Safo MK. J Struct Biol 194 446-450 (2016)


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  1. Direct observation of ligand migration within human hemoglobin at work. Shibayama N, Sato-Tomita A, Ohki M, Ichiyanagi K, Park SY. Proc Natl Acad Sci U S A 117 4741-4748 (2020)
  2. Structures and oxygen affinities of crystalline human hemoglobin C (β6 Glu->Lys) in the R and R2 quaternary structures. Shibayama N, Sugiyama K, Park SY. J Biol Chem 286 33661-33668 (2011)
  3. Sickle Cell Hemoglobin with Mutation at αHis-50 Has Improved Solubility. Tam MF, Tam TC, Simplaceanu V, Ho NT, Zou M, Ho C. J Biol Chem 290 21762-21772 (2015)
  4. Direct observation of conformational population shifts in crystalline human hemoglobin. Shibayama N, Ohki M, Tame JRH, Park SY. J Biol Chem 292 18258-18269 (2017)
  5. Novel Use of Hypoxia-Inducible Polymerizable Protein to Augment Chemotherapy for Pancreatic Cancer. Gdowski A, Hayatshahi H, Fudala R, Joshi R, Liu J, Vishwanatha JK, Jeyarajah R, Guzik P, Ranjan AP. Pharmaceutics 14 128 (2022)


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