1z8u
From Proteopedia
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| - | [[Image:1z8u.gif|left|200px]]<br /> | + | [[Image:1z8u.gif|left|200px]]<br /><applet load="1z8u" size="350" color="white" frame="true" align="right" spinBox="true" |
| - | <applet load="1z8u" size=" | + | |
caption="1z8u, resolution 2.4Å" /> | caption="1z8u, resolution 2.4Å" /> | ||
'''Crystal structure of oxidized alpha hemoglobin bound to AHSP'''<br /> | '''Crystal structure of oxidized alpha hemoglobin bound to AHSP'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The synthesis of haemoglobin A (HbA) is exquisitely coordinated during | + | The synthesis of haemoglobin A (HbA) is exquisitely coordinated during erythrocyte development to prevent damaging effects from individual alpha- and beta-subunits. The alpha-haemoglobin-stabilizing protein (AHSP) binds alpha-haemoglobin (alphaHb), inhibits the ability of alphaHb to generate reactive oxygen species and prevents its precipitation on exposure to oxidant stress. The structure of AHSP bound to ferrous alphaHb is thought to represent a transitional complex through which alphaHb is converted to a non-reactive, hexacoordinate ferric form. Here we report the crystal structure of this ferric alphaHb-AHSP complex at 2.4 A resolution. Our findings reveal a striking bis-histidyl configuration in which both the proximal and the distal histidines coordinate the haem iron atom. To attain this unusual conformation, segments of alphaHb undergo drastic structural rearrangements, including the repositioning of several alpha-helices. Moreover, conversion to the ferric bis-histidine configuration strongly and specifically inhibits redox chemistry catalysis and haem loss from alphaHb. The observed structural changes, which impair the chemical reactivity of haem iron, explain how AHSP stabilizes alphaHb and prevents its damaging effects in cells. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1Z8U 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 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1Z8U 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> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Z8U 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: HEM]] | [[Category: HEM]] | ||
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[[Category: oxidation]] | [[Category: oxidation]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:13:15 2008'' |
Revision as of 14:13, 21 February 2008
|
Crystal structure of oxidized alpha hemoglobin bound to AHSP
Contents |
Overview
The synthesis of haemoglobin A (HbA) is exquisitely coordinated during erythrocyte development to prevent damaging effects from individual alpha- and beta-subunits. The alpha-haemoglobin-stabilizing protein (AHSP) binds alpha-haemoglobin (alphaHb), inhibits the ability of alphaHb to generate reactive oxygen species and prevents its precipitation on exposure to oxidant stress. The structure of AHSP bound to ferrous alphaHb is thought to represent a transitional complex through which alphaHb is converted to a non-reactive, hexacoordinate ferric form. Here we report the crystal structure of this ferric alphaHb-AHSP complex at 2.4 A resolution. Our findings reveal a striking bis-histidyl configuration in which both the proximal and the distal histidines coordinate the haem iron atom. To attain this unusual conformation, segments of alphaHb undergo drastic structural rearrangements, including the repositioning of several alpha-helices. Moreover, conversion to the ferric bis-histidine configuration strongly and specifically inhibits redox chemistry catalysis and haem loss from alphaHb. The observed structural changes, which impair the chemical reactivity of haem iron, explain how AHSP stabilizes alphaHb and prevents its damaging effects in cells.
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
1Z8U is a Protein complex structure of sequences from Homo sapiens with as ligand. Full crystallographic information is available from OCA.
Reference
Structure of oxidized alpha-haemoglobin bound to AHSP reveals a protective mechanism for haem., Feng L, Zhou S, Gu L, Gell DA, Mackay JP, Weiss MJ, Gow AJ, Shi Y, Nature. 2005 Jun 2;435(7042):697-701. PMID:15931225
Page seeded by OCA on Thu Feb 21 16:13:15 2008
Categories: Homo sapiens | Protein complex | Feng, L. | Gell, D A. | Gow, A J. | Gu, L. | Mackay, J P. | Shi, Y. | Weiss, M J. | Zhou, S. | HEM | Ahsp | Alpha haemoglobin | Interaction | Oxidation
