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Structure of oxidized alpha-haemoglobin bound to AHSP reveals a protective mechanism for haem
Citation
Feng, L and Zhou, S and Gu, L and Gell, DA and Mackay, JP and Weiss, MJ and Gow, AJ and Shi, Y, Structure of oxidized alpha-haemoglobin bound to AHSP reveals a protective mechanism for haem, Nature: International Weekly Journal of Science, 435, (7042) pp. 697-701. ISSN 0028-0836 (2005) [Refereed Article]
Abstract
The synthesis of haemoglobin A (HbA) is exquisitely coordinated during erythrocyte development to prevent damaging effects from individual α- and β-subunits. The α-haemoglobin-stabilizing protein (AHSP) binds α-haemoglobin (αHb), inhibits the ability of αHb to generate reactive oxygen species and prevents its precipitation on exposure to oxidant stress. The structure of AHSP bound to ferrous αHb is thought to represent a transitional complex through which αHb is converted to a non-reactive, hexacoordinate ferric form. Here we report the crystal structure of this ferric αHb-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 αHb undergo drastic structural rearrangements, including the repositioning of several α-helices. Moreover, conversion to the ferric bishistidine configuration strongly and specifically inhibits redox chemistry catalysis and haem loss from αHb. The observed structural changes, which impair the chemical reactivity of haem iron, explain how AHSP stabilizes αHb and prevents its damaging effects in cells.
Item Details
Item Type: | Refereed Article |
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Research Division: | Biological Sciences |
Research Group: | Biochemistry and cell biology |
Research Field: | Structural biology (incl. macromolecular modelling) |
Objective Division: | Expanding Knowledge |
Objective Group: | Expanding knowledge |
Objective Field: | Expanding knowledge in the biological sciences |
UTAS Author: | Gell, DA (Dr David Gell) |
ID Code: | 64541 |
Year Published: | 2005 |
Web of Science® Times Cited: | 87 |
Deposited By: | Menzies Institute for Medical Research |
Deposited On: | 2010-08-12 |
Last Modified: | 2011-08-01 |
Downloads: | 0 |
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