1z8u | pdb_00001z8u
Crystal structure of oxidized alpha hemoglobin bound to AHSP
Structural highlights
FunctionAHSP_HUMAN Acts as a chaperone to prevent the harmful aggregation of alpha-hemoglobin during normal erythroid cell development. Specifically protects free alpha-hemoglobin from precipitation. It is predicted to modulate pathological states of alpha-hemoglobin excess such as beta-thalassemia.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedThe 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. 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[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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