@article{168441,
  keywords = {Animals, Models, Molecular, Crystallography, X-Ray, Protein Structure, Tertiary, Humans, Rats, Molecular Sequence Data, Sequence Homology, Nucleic Acid, Binding Sites, Histidine, Protein Binding, Macromolecular Substances, Sequence Homology, Amino Acid, Mice, Molecular Chaperones, Cattle, Sus scrofa, Nuclear Magnetic Resonance, Biomolecular, Protein Subunits, Enzyme Stability, Blood Proteins, Hemoglobin A, Iron, Oxyhemoglobins},
  author = {Liang Feng and David Gell and Suiping Zhou and Lichuan Gu and Yi Kong and Jianqing Li and Min Hu and Nieng Yan and Christopher Lee and Anne Rich and Robert Armstrong and Peter Lay and Andrew Gow and Mitchell Weiss and Joel Mackay and Yigong Shi},
  title = {Molecular mechanism of AHSP-mediated stabilization of alpha-hemoglobin},
  abstract = {<p>Hemoglobin A (HbA), the oxygen delivery system in humans, comprises two alpha and two beta subunits. Free alpha-hemoglobin (alphaHb) is unstable, and its precipitation contributes to the pathophysiology of beta thalassemia. In erythrocytes, the alpha-hemoglobin stabilizing protein (AHSP) binds alphaHb and inhibits its precipitation. The crystal structure of AHSP bound to Fe(II)-alphaHb reveals that AHSP specifically recognizes the G and H helices of alphaHb through a hydrophobic interface that largely recapitulates the alpha1-beta1 interface of hemoglobin. The AHSP-alphaHb interactions are extensive but suboptimal, explaining why beta-hemoglobin can competitively displace AHSP to form HbA. Remarkably, the Fe(II)-heme group in AHSP bound alphaHb is coordinated by the distal but not the proximal histidine. Importantly, binding to AHSP facilitates the conversion of oxy-alphaHb 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 alphaHb.</p>
},
  year = {2004},
  journal = {Cell},
  volume = {119},
  pages = {629-40},
  month = {11/2004},
  issn = {0092-8674},
  doi = {10.1016/j.cell.2004.11.025},
  language = {eng},
}