1HDB

ANALYSIS OF THE CRYSTAL STRUCTURE, MOLECULAR MODELING AND INFRARED SPECTROSCOPY OF THE DISTAL BETA-HEME POCKET VALINE67(E11)-THREONINE MUTATION OF HEMOGLOBIN

1HDB の概要

• エントリーDOI: 10.2210/pdb1hdb/pdb
• 分子名称: HEMOGLOBIN (DEOXY) BETA-V67T, PROTOPORPHYRIN IX CONTAINING FE, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: human hemoglobin, deoxy-beta-v67t, oxygen transport
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 64743.12

構造登録者

Pechik, I.,Ji, X.,Fronticelli, C.,Gilliland, G.L. (登録日: 1995-04-14, 公開日: 1996-04-03, 最終更新日: 2023-08-30)

主引用文献

Pechik, I.,Ji, X.,Fidelis, K.,Karavitis, M.,Moult, J.,Brinigar, W.S.,Fronticelli, C.,Gilliland, G.L.
Crystallographic, molecular modeling, and biophysical characterization of the valine beta 67 (E11)-->threonine variant of hemoglobin.
Biochemistry, 35:1935-1945, 1996

PubMed Abstract: The crystal structure of the mutant deoxyhemoglobin in which the beta-globin Val67(E11) has been replaced with threonine [Fronticelli et al. (1993) Biochemistry 32, 1235-1242] has been determined at 2.2 A resolution. Prior to the crystal structure determination, molecular modeling indicated that the Thr67(E11) side chain hydroxyl group in the distal beta-heme pocket forms a hydrogen bond with the backbone carbonyl of His63(E7) and is within hydrogen-bonding distance of the N delta of His63(E7). The mutant crystal structure indicates only small changes in conformation in the vicinity of the E11 mutation confirming the molecular modeling predictions. Comparison of the structures of the mutant beta-subunits and recombinant porcine myoglobin with the identical mutation [Cameron et al. (1993) Biochemistry 32, 13061-13070] indicates similar conformations of residues in the distal heme pocket, but there is no water molecule associated with either of the threonines of the beta-subunits. The introduction of threonine into the distal heme pocket, despite having only small perturbations in the local structure, has a marked affect on the interaction with ligands. In the oxy derivative there is a 2-fold decrease in O2 affinity [Fronticelli et al. (1993) Biochemistry 32, 1235-1242], and the rate of autoxidation is increased by 2 orders of magnitude. In the CO derivative the IR spectrum shows modifications with respect to that of normal human hemoglobin, suggesting the presence of multiple CO conformers. In the nitrosyl derivative an interaction with the O gamma atom of Thr67(E11) is probably responsible for the 10-fold increase in the rate of NO release from the beta-subunits. In the aquomet derivative there is a 6-fold decrease in the rate of hemin dissociation suggesting an interaction of the Fe-coordinated water with the O gamma of Thr67(E11).

PubMed: 8639677
DOI: 10.1021/bi9519967

実験手法

X-RAY DIFFRACTION (2.2 Å)