1z8u
From Proteopedia
(New page: 200px<br /> <applet load="1z8u" size="450" color="white" frame="true" align="right" spinBox="true" caption="1z8u, resolution 2.4Å" /> '''Crystal structure of...) |
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==Overview== | ==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. | 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. | ||
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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: oxidation]] | [[Category: oxidation]] | ||
| - | ''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 20:31:11 2007'' |
Revision as of 18:24, 12 November 2007
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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 HEM 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 Mon Nov 12 20:31:11 2007
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
