Suppr超能文献

远端组氨酸稳定结合的 O2,并作为配体进入成人血红蛋白两个亚基的门户。

Distal histidine stabilizes bound O2 and acts as a gate for ligand entry in both subunits of adult human hemoglobin.

机构信息

Department of Biochemistry and Cell Biology, W M Keck Center for Computational Biology, Rice University, Houston, Texas 77005, USA.

出版信息

J Biol Chem. 2010 Mar 19;285(12):8840-54. doi: 10.1074/jbc.M109.053934. Epub 2010 Jan 15.

Abstract

The role of the distal histidine in regulating ligand binding to adult human hemoglobin (HbA) was re-examined systematically by preparing His(E7) to Gly, Ala, Leu, Gln, Phe, and Trp mutants of both Hb subunits. Rate constants for O(2), CO, and NO binding were measured using rapid mixing and laser photolysis experiments designed to minimize autoxidation of the unstable apolar E7 mutants. Replacing His(E7) with Gly, Ala, Leu, or Phe causes 20-500-fold increases in the rates of O(2) dissociation from either Hb subunit, demonstrating unambiguously that the native His(E7) imidazole side chain forms a strong hydrogen bond with bound O(2) in both the alpha and beta chains (DeltaG(His(E7)H-bond) approximately -8 kJ/mol). As the size of the E7 amino acid is increased from Gly to Phe, decreases in k(O2)', k(NO)', and calculated bimolecular rates of CO entry (k(entry)') are observed. Replacing His(E7) with Trp causes further decreases in k(O2)', k(NO)', and k(entry)' to 1-2 microM(-1) s(-1) in beta subunits, whereas ligand rebinding to alphaTrp(E7) subunits after photolysis is markedly biphasic, with fast k(O2)', k(CO)', and k(NO)' values approximately 150 microM(-1) s(-1) and slow rate constants approximately 0.1 to 1 microM(-1) s(-1). Rapid bimolecular rebinding to an open alpha subunit conformation occurs immediately after photolysis of the alphaTrp(E7) mutant at high ligand concentrations. However, at equilibrium the closed alphaTrp(E7) side chain inhibits the rate of ligand binding >200-fold. These data suggest strongly that the E7 side chain functions as a gate for ligand entry in both HbA subunits.

摘要

重新系统地检查了远端组氨酸在调节成人血红蛋白 (HbA) 与配体结合中的作用,方法是制备 Hb 亚基的 His(E7) 至 Gly、Ala、Leu、Gln、Phe 和 Trp 突变体。使用快速混合和激光光解实验测量 O(2)、CO 和 NO 结合的速率常数,这些实验的设计旨在最小化不稳定的非极性 E7 突变体的自动氧化。用 Gly、Ala、Leu 或 Phe 取代 His(E7)会导致 O(2)从任一 Hb 亚基解离的速率增加 20-500 倍,这明确表明天然 His(E7)咪唑侧链在α和β链中与结合的 O(2)形成强氢键(DeltaG(His(E7)H-bond) 约为 -8 kJ/mol)。随着 E7 氨基酸的大小从 Gly 增加到 Phe,观察到 k(O2) '、k(NO) '和计算的 CO 进入的双分子速率 (k(entry) ') 降低。用 Trp 取代 His(E7)会导致β亚基中的 k(O2) '、k(NO) '和 k(entry) '进一步降低至 1-2 microM(-1) s(-1),而光解后 alphaTrp(E7)亚基的配体再结合明显呈双相,快速 k(O2) '、k(CO) '和 k(NO) '值约为 150 microM(-1) s(-1),缓慢的速率常数约为 0.1 至 1 microM(-1) s(-1)。在高配体浓度下,光解 alphaTrp(E7)突变体后,立即发生快速的双分子再结合到开放的 alpha 亚基构象。然而,在平衡时,封闭的 alphaTrp(E7)侧链抑制配体结合的速率 >200 倍。这些数据强烈表明,E7 侧链在 HbA 亚基中作为配体进入的门。

相似文献

1
Distal histidine stabilizes bound O2 and acts as a gate for ligand entry in both subunits of adult human hemoglobin.
J Biol Chem. 2010 Mar 19;285(12):8840-54. doi: 10.1074/jbc.M109.053934. Epub 2010 Jan 15.
4
Blocking the gate to ligand entry in human hemoglobin.
J Biol Chem. 2011 Mar 25;286(12):10515-29. doi: 10.1074/jbc.M110.176271. Epub 2010 Dec 29.
6
Characterization of recombinant soybean leghemoglobin a and apolar distal histidine mutants.
J Mol Biol. 1997 Mar 14;266(5):1032-42. doi: 10.1006/jmbi.1996.0833.
8
Modulating distal cavities in the α and β subunits of human HbA reveals the primary ligand migration pathway.
Biochemistry. 2011 Aug 30;50(34):7361-74. doi: 10.1021/bi200923k. Epub 2011 Aug 8.

引用本文的文献

1
Direct observation of two-channel photodissociation of carbon monoxide from the hemoglobin subunits.
Nat Commun. 2025 Aug 20;16(1):7746. doi: 10.1038/s41467-025-63092-z.
5
(4-(Adamantan-1-yl)-1-(isopropyl)-1-imidazol-2-yl)methanol.
Molbank. 2023 Mar;2023(1). doi: 10.3390/M1566. Epub 2023 Jan 23.
6
The Aer2 chemoreceptor from Vibrio vulnificus is a tri-PAS-heme oxygen sensor.
Mol Microbiol. 2023 Jan;119(1):59-73. doi: 10.1111/mmi.15007. Epub 2022 Dec 4.
7
Bioinformatic Characterization and Molecular Evolution of the Hemoglobins.
Genes (Basel). 2022 Nov 5;13(11):2041. doi: 10.3390/genes13112041.
8
Oxidative Implications of Substituting a Conserved Cysteine Residue in Sugar Beet Phytoglobin BvPgb 1.2.
Antioxidants (Basel). 2022 Aug 20;11(8):1615. doi: 10.3390/antiox11081615.
9
Impact of azole drugs on energetics, kinetics, and ligand migration pathways of CO photo-dissociation in bacterial flavohemoglobins.
RSC Adv. 2020 May 10;10(30):17930-17941. doi: 10.1039/d0ra02529a. eCollection 2020 May 5.
10
Kinetic mechanisms for O binding to myoglobins and hemoglobins.
Mol Aspects Med. 2022 Apr;84:101024. doi: 10.1016/j.mam.2021.101024. Epub 2021 Sep 17.

本文引用的文献

2
The apolar channel in Cerebratulus lacteus hemoglobin is the route for O2 entry and exit.
J Biol Chem. 2008 Dec 19;283(51):35689-702. doi: 10.1074/jbc.M805727200. Epub 2008 Oct 7.
3
Interfacial and distal-heme pocket mutations exhibit additive effects on the structure and function of hemoglobin.
Biochemistry. 2008 Oct 7;47(40):10551-63. doi: 10.1021/bi800816v. Epub 2008 Sep 13.
4
Toward quantitative simulations of carbon monoxide escape pathways in myoglobin.
J Phys Chem B. 2008 May 15;112(19):6147-54. doi: 10.1021/jp0769779. Epub 2008 Jan 19.
5
Ligand pathways in myoglobin: a review of Trp cavity mutations.
IUBMB Life. 2007 Aug-Sep;59(8-9):552-62. doi: 10.1080/15216540701230495.
6
1.25 A resolution crystal structures of human haemoglobin in the oxy, deoxy and carbonmonoxy forms.
J Mol Biol. 2006 Jul 14;360(3):690-701. doi: 10.1016/j.jmb.2006.05.036. Epub 2006 May 30.
7
Imaging the migration pathways for O2, CO, NO, and Xe inside myoglobin.
Biophys J. 2006 Sep 1;91(5):1844-57. doi: 10.1529/biophysj.106.085746. Epub 2006 Jun 2.
8
The origin of stark splitting in the initial photoproduct state of MbCO.
J Am Chem Soc. 2005 Jan 12;127(1):40-1. doi: 10.1021/ja0466917.
9
Measurement of rate constants for reactions of O2, CO, and NO with hemoglobin.
Methods Mol Med. 2003;82:65-91. doi: 10.1385/1-59259-373-9:065.

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验