1y01
From Proteopedia
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| - | [[Image:1y01.gif|left|200px]]<br /> | + | [[Image:1y01.gif|left|200px]]<br /><applet load="1y01" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1y01" size=" | + | |
caption="1y01, resolution 2.8Å" /> | caption="1y01, resolution 2.8Å" /> | ||
'''Crystal structure of AHSP bound to Fe(II) alpha-hemoglobin'''<br /> | '''Crystal structure of AHSP bound to Fe(II) alpha-hemoglobin'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Hemoglobin A (HbA), the oxygen delivery system in humans, comprises two | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1Y01 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with HEM, OXY and CHK as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http:// | + | 1Y01 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=HEM:'>HEM</scene>, <scene name='pdbligand=OXY:'>OXY</scene> and <scene name='pdbligand=CHK:'>CHK</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Y01 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Protein complex]] | [[Category: Protein complex]] | ||
[[Category: Feng, L.]] | [[Category: Feng, L.]] | ||
| - | [[Category: Gell, D | + | [[Category: Gell, D A.]] |
| - | [[Category: Gow, A | + | [[Category: Gow, A J.]] |
[[Category: Gu, L.]] | [[Category: Gu, L.]] | ||
| - | [[Category: Mackay, J | + | [[Category: Mackay, J P.]] |
[[Category: Shi, Y.]] | [[Category: Shi, Y.]] | ||
| - | [[Category: Weiss, M | + | [[Category: Weiss, M J.]] |
[[Category: Zhou, S.]] | [[Category: Zhou, S.]] | ||
[[Category: CHK]] | [[Category: CHK]] | ||
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[[Category: stabilization of alpha hemoglobin]] | [[Category: stabilization of alpha hemoglobin]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:00:26 2008'' |
Revision as of 14:00, 21 February 2008
|
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 , and 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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