1I3D

HUMAN CARBONMONOXY HEMOGLOBIN BART'S (GAMMA4)

1I3D の概要

• エントリーDOI: 10.2210/pdb1i3d/pdb
• 関連するPDBエントリー: 1I3E
• 分子名称: HEMOGLOBIN GAMMA CHAINS, PROTOPORPHYRIN IX CONTAINING FE, CARBON MONOXIDE, ... (4 entities in total)
• 機能のキーワード: oxygen transport, oxygen storage-transport complex, oxygen storage/transport
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 33351.50

構造登録者

Kidd, R.D.,Baker, H.M.,Mathews, A.J.,Brittain, T.,Baker, E.N. (登録日: 2001-02-15, 公開日: 2001-09-12, 最終更新日: 2023-08-09)

主引用文献

Kidd, R.D.,Baker, H.M.,Mathews, A.J.,Brittain, T.,Baker, E.N.
Oligomerization and ligand binding in a homotetrameric hemoglobin: two high-resolution crystal structures of hemoglobin Bart's (gamma(4)), a marker for alpha-thalassemia.
Protein Sci., 10:1739-1749, 2001

PubMed Abstract: Hemoglobin (Hb) Bart's is present in the red blood cells of millions of people worldwide who suffer from alpha-thalassemia. alpha-Thalassemia is a disease in which there is a deletion of one or more of the four alpha-chain genes, and excess gamma and beta chains spontaneously form homotetramers. The gamma(4) homotetrameric protein known as Hb Bart's is a stable species that exhibits neither a Bohr effect nor heme-heme cooperativity. Although Hb Bart's has a higher O(2) affinity than either adult (alpha(2)beta(2)) or fetal (alpha(2)gamma(2)) Hbs, it has a lower affinity for O(2) than HbH (beta(4)). To better understand the association and ligand binding properties of the gamma(4) tetramer, we have solved the structure of Hb Bart's in two different oxidation and ligation states. The crystal structure of ferrous carbonmonoxy (CO) Hb Bart's was determined by molecular replacement and refined at 1.7 A resolution (R = 21.1%, R(free) = 24.4%), and that of ferric azide (N(3)(-)) Hb Bart's was similarly determined at 1.86 A resolution (R = 18.4%, R(free) = 22.0%). In the carbonmonoxy-Hb structure, the CO ligand is bound at an angle of 140 degrees, and with an unusually long Fe-C bond of 2.25 A. This geometry is attributed to repulsion from the distal His63 at the low pH of crystallization (4.5). In contrast, azide is bound to the oxidized heme iron in the methemoglobin crystals at an angle of 112 degrees, in a perfect orientation to accept a hydrogen bond from His63. Compared to the three known quaternary structures of human Hb (T, R, and R2), both structures most closely resemble the R state. Comparisons with the structures of adult Hb and HbH explain the association and dissociation behaviour of Hb homotetramers relative to the heterotetrameric Hbs.

PubMed: 11514664
DOI: 10.1110/ps.11701

実験手法

X-RAY DIFFRACTION (1.7 Å)