1y01
From Proteopedia
(New page: 200px<br /> <applet load="1y01" size="450" color="white" frame="true" align="right" spinBox="true" caption="1y01, resolution 2.8Å" /> '''Crystal structure of...) |
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==Overview== | ==Overview== | ||
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. | 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. | ||
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| + | ==Disease== | ||
| + | Known diseases associated with this structure: Erythremias, alpha- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141800 141800]], Erythrocytosis OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141850 141850]], Heinz body anemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141850 141850]], Heinz body anemias, alpha- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141800 141800]], Hemoglobin H disease OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141850 141850]], Hypochromic microcytic anemia OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141850 141850]], Methemoglobinemias, alpha- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141800 141800]], Thalassemia, alpha- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141850 141850]], Thalassemias, alpha- OMIM:[[http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=141800 141800]] | ||
==About this Structure== | ==About this Structure== | ||
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[[Category: stabilization of alpha hemoglobin]] | [[Category: stabilization of alpha hemoglobin]] | ||
| - | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:12:57 2007'' |
Revision as of 18:06, 12 November 2007
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Crystal structure of AHSP bound to Fe(II) alpha-hemoglobin
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Erythremias, alpha- OMIM:[141800], Erythrocytosis OMIM:[141850], Heinz body anemia OMIM:[141850], Heinz body anemias, alpha- OMIM:[141800], Hemoglobin H disease OMIM:[141850], Hypochromic microcytic anemia OMIM:[141850], Methemoglobinemias, alpha- OMIM:[141800], Thalassemia, alpha- OMIM:[141850], Thalassemias, alpha- OMIM:[141800]
About this Structure
1Y01 is a Protein complex structure of sequences from Homo sapiens with HEM, OXY and CHK as ligands. Full crystallographic information is available from OCA.
Reference
Molecular mechanism of AHSP-mediated stabilization of alpha-hemoglobin., Feng L, Gell DA, Zhou S, Gu L, Kong Y, Li J, Hu M, Yan N, Lee C, Rich AM, Armstrong RS, Lay PA, Gow AJ, Weiss MJ, Mackay JP, Shi Y, Cell. 2004 Nov 24;119(5):629-40. PMID:15550245
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