1Z8U

Crystal structure of oxidized alpha hemoglobin bound to AHSP

Summary for 1Z8U

• Entry DOI: 10.2210/pdb1z8u/pdb
• Related: 1Y01
• Descriptor: Alpha-hemoglobin stabilizing protein, Hemoglobin alpha chain, PROTOPORPHYRIN IX CONTAINING FE, ... (4 entities in total)
• Functional Keywords: alpha haemoglobin, ahsp, oxidation, interaction, electron transport
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: Q9NZD4
• Total number of polymer chains: 4
• Total formula weight: 55448.73

Authors

Feng, L.,Zhou, S.,Gu, L.,Gell, D.A.,Mackay, J.P.,Weiss, M.J.,Gow, A.J.,Shi, Y. (deposition date: 2005-03-31, release date: 2005-06-14, Last modification date: 2024-02-14)

Primary citation

Feng, L.,Zhou, S.,Gu, L.,Gell, D.A.,Mackay, J.P.,Weiss, M.J.,Gow, A.J.,Shi, Y.
Structure of oxidized alpha-haemoglobin bound to AHSP reveals a protective mechanism for haem.
Nature, 435:697-701, 2005

PubMed Abstract: 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.

PubMed: 15931225
DOI: 10.1038/nature03609

Experimental method

X-RAY DIFFRACTION (2.4 Å)