1y01: Difference between revisions

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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="450" color="white" frame="true" align="right" spinBox="true"  
caption="1y01, resolution 2.8&Aring;" />
caption="1y01, resolution 2.8&Aring;" />
'''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, 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.


==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://ispc.weizmann.ac.il/oca-bin/ocashort?id=1Y01 OCA].  
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.A.]]
[[Category: Gell, D A.]]
[[Category: Gow, A.J.]]
[[Category: Gow, A J.]]
[[Category: Gu, L.]]
[[Category: Gu, L.]]
[[Category: Mackay, J.P.]]
[[Category: Mackay, J P.]]
[[Category: Shi, Y.]]
[[Category: Shi, Y.]]
[[Category: Weiss, M.J.]]
[[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://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 20:12:57 2007''
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:00:26 2008''