1xzy
From Proteopedia
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==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. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Feng, L.]] | [[Category: Feng, L.]] | ||
| - | [[Category: Gell, D | + | [[Category: Gell, D A.]] |
[[Category: Kong, Y.]] | [[Category: Kong, Y.]] | ||
[[Category: Lee, C.]] | [[Category: Lee, C.]] | ||
| - | [[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: helical bundle]] | [[Category: helical bundle]] | ||
[[Category: three-helix bundle]] | [[Category: three-helix bundle]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:00:24 2008'' |
Revision as of 14:00, 21 February 2008
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Solution structure of the P30-trans form of Alpha Hemoglobin Stabilizing Protein (AHSP)
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.
About this Structure
1XZY is a Single protein structure of sequence from Homo sapiens. 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
Page seeded by OCA on Thu Feb 21 16:00:24 2008
Categories: Homo sapiens | Single protein | Feng, L. | Gell, D A. | Kong, Y. | Lee, C. | Mackay, J P. | Shi, Y. | Weiss, M J. | Zhou, S. | Helical bundle | Three-helix bundle
