1VWT

T STATE HUMAN HEMOGLOBIN [ALPHA V96W], ALPHA AQUOMET, BETA DEOXY

1VWT の概要

• エントリーDOI: 10.2210/pdb1vwt/pdb
• 分子名称: HEMOGLOBIN, PROTOPORPHYRIN IX CONTAINING FE, SULFATE ION, ... (5 entities in total)
• 機能のキーワード: oxygen transport, hemoglobin, human, mutant, alpha-(v96w), deoxy, deoxy hemoglobin, met hemoglobin
• 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: 64913.34

構造登録者

Puius, Y.A.,Zou, M.,Ho, N.T.,Ho, C.,Almo, S.C. (登録日: 1997-03-20, 公開日: 1998-03-25, 最終更新日: 2024-05-22)

主引用文献

Puius, Y.A.,Zou, M.,Ho, N.T.,Ho, C.,Almo, S.C.
Novel water-mediated hydrogen bonds as the structural basis for the low oxygen affinity of the blood substitute candidate rHb(alpha 96Val-->Trp).
Biochemistry, 37:9258-9265, 1998

PubMed Abstract: One of the most promising approaches for the development of a synthetic blood substitute has been the engineering of novel mutants of human hemoglobin (Hb) A which maintain cooperativity, but possess lowered oxygen affinity. We describe here two crystal structures of one such potential blood substitute, recombinant (r) Hb(alpha 96Val-->Trp), refined to 1.9 A resolution in an alpha-aquomet, beta-deoxy T-state, and to 2.5 A resolution in a carbonmonoxy R-state. On the basis of molecular dynamics simulations, a particular conformation had been predicted for the engineered Trp residue, and the lowered oxygen affinity had been attributed to a stabilization of the deoxy T-state interface by alpha 96Trp-beta 99Asp hydrogen bonds. Difference Fourier maps of the T-state structure clearly show that alpha 96Trp is in a conformation different from that predicted by the simulation, with its indole side chain directed away from the interface and into the central cavity. In this conformation, the indole nitrogen makes novel water-mediated hydrogen bonds across the T-state interface with beta 101Glu. We propose that these water-mediated hydrogen bonds are the structural basis for the lowered oxygen affinity of rHb(alpha 96Val-->Trp), and discuss the implications of these findings for future molecular dynamics studies and the design of Hb mutants.

PubMed: 9649306
DOI: 10.1021/bi9727287

実験手法

X-RAY DIFFRACTION (1.9 Å)