2AV0

F97L with CO bound

「3HBI」から置き換えられました

2AV0 の概要

• エントリーDOI: 10.2210/pdb2av0/pdb
• 関連するPDBエントリー: 2AUO 2AUP 2AUQ 2AUR 2AV3 2HBI 3HBI
• 分子名称: Globin I, PROTOPORPHYRIN IX CONTAINING FE, CARBON MONOXIDE, ... (4 entities in total)
• 機能のキーワード: oxygen transport, oxygen binding, allosteric, hemoglobin, oxygen storage-transport complex, oxygen storage/transport
• 由来する生物種: Scapharca inaequivalvis (ark clam)
• 細胞内の位置: Cytoplasm: P02213
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 33155.57

構造登録者

Knapp, J.E.,Bonham, M.A.,Gibson, Q.H.,Nichols, J.C.,Royer Jr., W.E. (登録日: 2005-08-29, 公開日: 2006-03-28, 最終更新日: 2023-08-23)

主引用文献

Knapp, J.E.,Bonham, M.A.,Gibson, Q.H.,Nichols, J.C.,Royer Jr., W.E.
Residue F4 plays a key role in modulating oxygen affinity and cooperativity in Scapharca dimeric hemoglobin
Biochemistry, 44:14419-14430, 2005

PubMed Abstract: Residue F4 (Phe 97) undergoes the most dramatic ligand-linked transition in Scapharca dimeric hemoglobin, with its packing in the heme pocket in the unliganded (T) state suggested to be a primary determinant of its low affinity. Mutation of Phe 97 to Leu (previously reported), Val, and Tyr increases oxygen affinity from 8- to 100-fold over that of the wild type. The crystal structures of F97L and F97V show side chain packing in the heme pocket for both R and T state structures. In contrast, in the highest-affinity mutation, F97Y, the tyrosine side chain remains in the interface (high-affinity conformation) even in the unliganded state. Comparison of these mutations reveals a correlation between side chain packing in the heme pocket and oxygen affinity, indicating that greater mass in the heme pocket lowers oxygen affinity due to impaired movement of the heme iron into the heme plane. The results indicate that a key hydrogen bond, previously hypothesized to have a central role in regulation of oxygen affinity, plays at most only a small role in dictating ligand affinity. Equivalent mutations in sperm whale myoglobin alter ligand affinity by only 5-fold. The dramatically different responses to mutations at the F4 position result from subtle, but functionally critical, stereochemical differences. In myoglobin, an eclipsed orientation of the proximal His relative to the A and C pyrrole nitrogen atoms provides a significant barrier for high-affinity ligand binding. In contrast, the staggered orientation of the proximal histidine found in liganded HbI renders its ligand affinity much more susceptible to packing contacts between F4 and the heme group. These results highlight very different strategies used by cooperative hemoglobins in molluscs and mammals to control ligand affinity by modulation of the stereochemistry on the proximal side of the heme.

PubMed: 16262242
DOI: 10.1021/bi051052+

実験手法

X-RAY DIFFRACTION (1.5 Å)