血红蛋白：结构、功能与别构效应
Hemoglobin: Structure, Function and Allostery.
作者信息
Ahmed Mostafa H, Ghatge Mohini S, Safo Martin K
机构信息
Department of Medicinal Chemistry, School of Pharmacy, Virginia Commonwealth University, Richmond, VA, 23219, USA.
Institute for Structural Biology, Drug Discovery and Development, Virginia Commonwealth University, Richmond, VA, 23219, USA.
出版信息
Subcell Biochem. 2020;94:345-382. doi: 10.1007/978-3-030-41769-7_14.
Abstract
This chapter reviews how allosteric (heterotrophic) effectors and natural mutations impact hemoglobin (Hb) primary physiological function of oxygen binding and transport. First, an introduction about the structure of Hb is provided, including the ensemble of tense and relaxed Hb states and the dynamic equilibrium of Hb multistate. This is followed by a brief review of Hb variants with altered Hb structure and oxygen binding properties. Finally, a review of different endogenous and exogenous allosteric effectors of Hb is presented with particular emphasis on the atomic interactions of synthetic ligands with altered allosteric function of Hb that could potentially be harnessed for the treatment of diseases.
摘要
本章回顾了变构（异养）效应物和自然突变如何影响血红蛋白（Hb）结合和运输氧气的主要生理功能。首先，介绍了Hb的结构，包括紧张态和松弛态Hb的整体结构以及Hb多态的动态平衡。接下来简要回顾了具有改变的Hb结构和氧结合特性的Hb变体。最后，介绍了不同的Hb内源性和外源性变构效应物，特别强调了具有改变的Hb变构功能的合成配体的原子相互作用，这些相互作用可能被用于疾病治疗。
相似文献
1
Hemoglobin: Structure, Function and Allostery.血红蛋白：结构、功能与别构效应
Subcell Biochem. 2020;94:345-382. doi: 10.1007/978-3-030-41769-7_14.
2
Hemoglobin-ligand binding: understanding Hb function and allostery on atomic level.血红蛋白-配体结合：在原子水平上理解血红蛋白的功能和变构效应。
Biochim Biophys Acta. 2011 Jun;1814(6):797-809. doi: 10.1016/j.bbapap.2011.02.013. Epub 2011 Mar 8.
3
Protein dynamics explain the allosteric behaviors of hemoglobin.蛋白质动力学解释了血红蛋白的变构行为。
Biochim Biophys Acta. 2008 Sep;1784(9):1146-58. doi: 10.1016/j.bbapap.2008.04.025. Epub 2008 May 8.
4
Structure of relaxed-state human hemoglobin: insight into ligand uptake, transport and release.松弛态人血红蛋白的结构：对配体摄取、运输和释放的见解。
Acta Crystallogr D Biol Crystallogr. 2009 Jan;65(Pt 1):41-8. doi: 10.1107/S0907444908037256. Epub 2008 Dec 18.
5
Ligand binding properties and structural studies of recombinant and chemically modified hemoglobins altered at beta 93 cysteine.β93位半胱氨酸发生改变的重组及化学修饰血红蛋白的配体结合特性与结构研究
Biochemistry. 2002 Oct 1;41(39):11901-13. doi: 10.1021/bi0202880.
6
Non-Allosteric Cooperativity in Hemoglobin.血红蛋白中的非别构协同性。
Curr Protein Pept Sci. 2018;19(6):573-588. doi: 10.2174/1389203718666171030103310.
7
How does hemoglobin generate such diverse functionality of physiological relevance?血红蛋白是如何产生如此多样的具有生理相关性的功能的？
Biochim Biophys Acta. 2013 Sep;1834(9):1873-84. doi: 10.1016/j.bbapap.2013.04.026. Epub 2013 May 1.
8
Capturing the hemoglobin allosteric transition in a single crystal form.捕获血红蛋白变构转变的单晶形式。
J Am Chem Soc. 2014 Apr 2;136(13):5097-105. doi: 10.1021/ja500380e. Epub 2014 Mar 24.
9
Polyphosphates and pyrophosphates of pentopyranoses and pentofuranoses as allosteric effectors of human hemoglobin: synthesis, molecular recognition, and oxygen release.五吡喃糖和五呋喃糖的多磷酸盐和焦磷酸盐作为人血红蛋白的别构效应物：合成、分子识别和氧释放。
ChemMedChem. 2011 Aug 1;6(8):1495-508. doi: 10.1002/cmdc.201100110. Epub 2011 Jun 14.
10
Structure of fully liganded Hb ζ2β2s trapped in a tense conformation.被困于紧张构象的完全配体化的血红蛋白ζ2β2s的结构。
Acta Crystallogr D Biol Crystallogr. 2013 Oct;69(Pt 10):2061-71. doi: 10.1107/S0907444913019197. Epub 2013 Sep 20.
引用本文的文献
1
A functional and applied perspective of Vitreoscilla hemoglobin: from oxygen carriage to biotechnological innovation.透明颤菌血红蛋白的功能与应用视角：从氧气运输到生物技术创新
Biotechnol Lett. 2025 Sep 4;47(5):94. doi: 10.1007/s10529-025-03635-y.
2
Increased Exercise Tolerance in G6PD African Variant Mice Driven by Metabolic Adaptations and Erythrophagocytosis.代谢适应和红细胞吞噬作用驱动的G6PD非洲变异小鼠运动耐力增强。
Antioxidants (Basel). 2025 Jul 29;14(8):927. doi: 10.3390/antiox14080927.
3
The association between hemoglobin-to-red cell distribution width ratio and asthma and asthma exacerbations: a cross-sectional study.血红蛋白与红细胞分布宽度比值与哮喘及哮喘急性加重之间的关联：一项横断面研究。
BMC Pulm Med. 2025 Aug 21;25(1):400. doi: 10.1186/s12890-025-03852-1.
4
The interactions of non-functionalized polystyrene nanoparticles with human albumin and erythrocyte proteins: implications and potential consequences.非功能化聚苯乙烯纳米颗粒与人类白蛋白和红细胞蛋白的相互作用：影响及潜在后果
Sci Rep. 2025 Aug 17;15(1):30076. doi: 10.1038/s41598-025-15422-w.
5
Current understanding of eryptosis: mechanisms, physiological functions, role in disease, pharmacological applications, and nomenclature recommendations.红细胞凋亡的当前认识：机制、生理功能、在疾病中的作用、药理学应用及命名建议
Cell Death Dis. 2025 Jul 1;16(1):467. doi: 10.1038/s41419-025-07784-w.
6
Yak () Meat Peptides: Effects on Immunity, Hypoxia Tolerance, and Antioxidant Capacity in Hypotonic Hypoxia Mice.牦牛肉肽：对低氧性低氧小鼠免疫、耐缺氧及抗氧化能力的影响
Food Sci Nutr. 2025 Jun 27;13(7):e70522. doi: 10.1002/fsn3.70522. eCollection 2025 Jul.
7
Functional Requirement of Niacinamide for Blood Profiles, Antioxidant Status, and Intestinal Health in Finishing Pigs Fed a Low-Protein Diet.低蛋白日粮育肥猪中烟酰胺对血液指标、抗氧化状态和肠道健康的功能需求
Animals (Basel). 2025 Jun 19;15(12):1813. doi: 10.3390/ani15121813.
8
'Intelligent' proteins.“智能”蛋白质。
Cell Mol Life Sci. 2025 Jun 14;82(1):239. doi: 10.1007/s00018-025-05770-1.
9
Iron deficiency anemia in pregnancy and related complications with specific insight in Rivers State, Nigeria: a narrative review.尼日利亚河流州妊娠期缺铁性贫血及其相关并发症的具体见解：叙述性综述
Ann Med Surg (Lond). 2025 Apr 2;87(6):3435-3444. doi: 10.1097/MS9.0000000000003224. eCollection 2025 Jun.
10
Hemoglobin-to-Red Cell Distribution Width Ratio as a Predictor of Gastrointestinal Bleeding Following Percutaneous Coronary Intervention.血红蛋白与红细胞分布宽度比值作为经皮冠状动脉介入治疗后胃肠道出血的预测指标
Cardiol Res Pract. 2025 Apr 27;2025:2793810. doi: 10.1155/crp/2793810. eCollection 2025.
本文引用的文献
1
A Phase 3 Randomized Trial of Voxelotor in Sickle Cell Disease.一项针对镰状细胞病患者的 voxotor 的 3 期随机试验。
N Engl J Med. 2019 Aug 8;381(6):509-519. doi: 10.1056/NEJMoa1903212. Epub 2019 Jun 14.
2
Alternate and Additional Functions of Erythrocyte Hemoglobin.红细胞血红蛋白的交替功能和附加功能。
Biochemistry (Mosc). 2018 Dec;83(12):1575-1593. doi: 10.1134/S0006297918120155.
3
Rational modification of vanillin derivatives to stereospecifically destabilize sickle hemoglobin polymer formation.合理修饰香草醛衍生物以立体特异性破坏镰状血红蛋白聚合物的形成。
Acta Crystallogr D Struct Biol. 2018 Oct 1;74(Pt 10):956-964. doi: 10.1107/S2059798318009919. Epub 2018 Oct 2.
4
Design, Synthesis, and Biological Evaluation of Allosteric Effectors That Enhance CO Release from Carboxyhemoglobin.增强一氧化碳从羧基血红蛋白释放的变构效应剂的设计、合成及生物学评价
ACS Med Chem Lett. 2018 May 11;9(7):714-718. doi: 10.1021/acsmedchemlett.8b00166. eCollection 2018 Jul 12.
5
Rational design of pyridyl derivatives of vanillin for the treatment of sickle cell disease.基于香草醛的吡啶基衍生物的合理设计用于治疗镰状细胞病。
Bioorg Med Chem. 2018 May 15;26(9):2530-2538. doi: 10.1016/j.bmc.2018.04.015. Epub 2018 Apr 6.
6
A Triazole Disulfide Compound Increases the Affinity of Hemoglobin for Oxygen and Reduces the Sickling of Human Sickle Cells.三氮唑二硫化合物增加血红蛋白对氧气的亲和力并减少人类镰状细胞的镰状化。
Mol Pharm. 2018 May 7;15(5):1954-1963. doi: 10.1021/acs.molpharmaceut.8b00108. Epub 2018 Apr 18.
7
Understanding the molecular basis of the high oxygen affinity variant human hemoglobin Coimbra.了解高氧亲和力变异型人类血红蛋白科英布拉的分子基础。
Arch Biochem Biophys. 2018 Jan 1;637:73-78. doi: 10.1016/j.abb.2017.11.010. Epub 2017 Dec 1.
8
Structural and Functional Insight of Sphingosine 1-Phosphate-Mediated Pathogenic Metabolic Reprogramming in Sickle Cell Disease.鞘氨醇 1-磷酸介导的镰状细胞病致病代谢重编程的结构和功能见解。
Sci Rep. 2017 Nov 10;7(1):15281. doi: 10.1038/s41598-017-13667-8.
9
Structure and function of haemoglobins.血红蛋白的结构与功能。
Blood Cells Mol Dis. 2018 May;70:13-42. doi: 10.1016/j.bcmd.2017.10.006. Epub 2017 Oct 31.
10
Design, Synthesis, and Biological Evaluation of Ester and Ether Derivatives of Antisickling Agent 5-HMF for the Treatment of Sickle Cell Disease.抗镰状细胞病药物 5-HMF 的酯和醚衍生物的设计、合成及生物学评价。
Mol Pharm. 2017 Oct 2;14(10):3499-3511. doi: 10.1021/acs.molpharmaceut.7b00553. Epub 2017 Sep 13.
Zotero 插件