Molecular mechanism of AHSP-mediated stabilization of α-hemoglobin. Feng, L., Gell, D., Zhou, S., Gu, L., Kong, Y., Li, J., Hu, M., Yan, N., Lee, C., Rich, A., Armstrong, R., Lay, P., Gow, A., Weiss, M., MacKay, J., & Shi, Y. Cell, 119(5):629-640, Elsevier B.V., 2004. cited By 134![Molecular mechanism of AHSP-mediated stabilization of α-hemoglobin [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex Hemoglobin A (HbA), the oxygen delivery system in humans, comprises two α and two β subunits. Free α-hemoglobin (αHb) is unstable, and its precipitation contributes to the pathophysiology of β thalassemia. In erythrocytes, the α-hemoglobin stabilizing protein (AHSP) binds αHb and inhibits its precipitation. The crystal structure of AHSP bound to Fe(II)-αHb reveals that AHSP specifically recognizes the G and H helices of αHb through a hydrophobic interface that largely recapitulates the α1-β1 interface of hemoglobin. The AHSP-αHb interactions are extensive but suboptimal, explaining why β-hemoglobin can competitively displace AHSP to form HbA. Remarkably, the Fe(II)-heme group in AHSP bound αHb is coordinated by the distal but not the proximal histidine. Importantly, binding to AHSP facilitates the conversion of oxy-αHb to a deoxygenated, oxidized [Fe(III)], nonreactive form in which all six coordinate positions are occupied. These observations reveal the molecular mechanisms by which AHSP stabilizes free αHb.
@ARTICLE{Feng2004629,
author={Feng, L. and Gell, D.A. and Zhou, S. and Gu, L. and Kong, Y. and Li, J. and Hu, M. and Yan, N. and Lee, C. and Rich, A.M. and Armstrong, R.S. and Lay, P.A. and Gow, A.J. and Weiss, M.J. and MacKay, J.P. and Shi, Y.},
title={Molecular mechanism of AHSP-mediated stabilization of α-hemoglobin},
journal={Cell},
year={2004},
volume={119},
number={5},
pages={629-640},
doi={10.1016/j.cell.2004.11.025},
note={cited By 134},
url={https://www.scopus.com/inward/record.uri?eid=2-s2.0-8844285199&doi=10.1016%2fj.cell.2004.11.025&partnerID=40&md5=27f288dcb2581a94812fe009ea36514c},
affiliation={Department of Molecular Biology, Lewis Thomas Laboratory, Princeton University, 08544, Princeton, NJ, United States; Sch. of Molec. and Microbial Biosci., University of Sydney, NSW 2006, Sydney, Australia; Children's Hosp. Philadelphia U., Philadelphia, PA, United States; Ctr. Heavy Met. Res. Ctr. Struct. B., School of Chemistry, University of Sydney, NSW 2006, Sydney, Australia},
abstract={Hemoglobin A (HbA), the oxygen delivery system in humans, comprises two α and two β subunits. Free α-hemoglobin (αHb) is unstable, and its precipitation contributes to the pathophysiology of β thalassemia. In erythrocytes, the α-hemoglobin stabilizing protein (AHSP) binds αHb and inhibits its precipitation. The crystal structure of AHSP bound to Fe(II)-αHb reveals that AHSP specifically recognizes the G and H helices of αHb through a hydrophobic interface that largely recapitulates the α1-β1 interface of hemoglobin. The AHSP-αHb interactions are extensive but suboptimal, explaining why β-hemoglobin can competitively displace AHSP to form HbA. Remarkably, the Fe(II)-heme group in AHSP bound αHb is coordinated by the distal but not the proximal histidine. Importantly, binding to AHSP facilitates the conversion of oxy-αHb to a deoxygenated, oxidized [Fe(III)], nonreactive form in which all six coordinate positions are occupied. These observations reveal the molecular mechanisms by which AHSP stabilizes free αHb.},
keywords={alpha hemoglobin; alpha hemoglobin stabilizing protein; heme; hemoglobin; histidine; iron; protein; unclassified drug, article; crystal structure; deoxygenation; erythrocyte; hydrophobicity; oxidation; precipitation; priority journal; protein binding; protein stability, Oxy},
correspondence_address1={Weiss, M.J.; Children's Hosp. Philadelphia U., Philadelphia, PA, United States; email: yshi@molbio.princeton.edu},
publisher={Elsevier B.V.},
issn={00928674},
coden={CELLB},
pubmed_id={15550245},
language={English},
abbrev_source_title={Cell},
document_type={Article},
source={Scopus},
}
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