Haemoglobin: The structural changes related to ligand binding and its allosteric mechanism
TL;DR: These structural results, together with other work, particularly the calculations of Gelin & Karplus and of Warshel, support a description of the haemoglobin mechanism in which the binding of ligand to the deoxy form is accompanied by steric strain, so that the proportion of molecules in the high-affinity form increases as successive ligands bind.
About: This article is published in Journal of Molecular Biology.The article was published on 1979-04-05. It has received 802 citations till now. The article focuses on the topics: Protein quaternary structure & Helix.
Citations
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TL;DR: The crystal structure of Pseudomonas putida cytochrome P450 with its substrate, camphor, bound has been refined to R = 0.19 at a normal resolution of 1.63 A as discussed by the authors.
1,352 citations
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TL;DR: To determine how different amino acid sequences form similar protein structures, and how proteins adapt to mutations that change the volume of residues buried in their close-packed interiors, the atomic structures of nine different globins are analysed and compared.
697 citations
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TL;DR: The structure of human deoxyhaemoglobin was refined at 1.74 A resolution using data collected on film at room temperature from a synchrotron X-ray source and the effects of intermolecular contacts on the structure were investigated.
621 citations
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TL;DR: The structure of oxymyoglobin has been refined at 1·6 A resolution, using diffractometer data collected at −12 °C, and movements of the haem, iron, F helix and FG corner on oxygenation are similar to those found in the T-R state transition in haemoglobin, but are smaller in magnitude.
604 citations
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TL;DR: The chapter discusses the thermodynamic and kinetic studies of solutions, and includes a description of the nonideal behavior of concentrated hemoglobin S solutions and the effects of physiologically relevant variables, especially oxygen, and the presence of non-S hemoglobins on the polymerization process.
Abstract: Publisher Summary The chapter describes the understanding of the physics and physical chemistry of sickle cell hemoglobin polymerization in solutions and in red cells. The polymerization of sickle cell hemoglobin has probably become the best understood of all protein self-assembly systems. The structure of the hemoglobin S molecule, the structure of the various aggregated forms of hemoglobin S, and the structural analysis of the polymers are discussed in the chapter. The chapter discusses the thermodynamics of hemoglobin S polymerization, and includes a description of the nonideal behavior of concentrated hemoglobin S solutions and the effects of physiologically relevant variables, especially oxygen, and the presence of non-S hemoglobins on the polymerization process. Understanding the polymerization process is not only important for understanding the pathophysiology of sickle cell disease, but is critical to the major problem of developing a specific therapy that could be used in the treatment of patients. The kinetic and thermodynamic studies have played a major role by providing relevant and sensitive assays for potential therapeutic agents. The results of the thermodynamic and kinetic studies of solutions are used to explain various properties of cells, including morphological and rheological properties.
578 citations
References
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TL;DR: "It is certain that all bodies whatsoever, though they have no sense, yet they have perception, and whether the body be alterant or alterec, evermore a perception precedeth operation; for else all bodies would be like one to another."
8,157 citations
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TL;DR: The oxygenation of haemoglobin is accompanied by structural changes in the subunits triggered by shifts of the iron atoms relative to the porphyrin and, in the β-subunits, also by the steric effect of oxygen itself.
Abstract: The oxygenation of haemoglobin is accompanied by structural changes in the subunits triggered by shifts of the iron atoms relative to the porphyrin and, in the β-subunits, also by the steric effect of oxygen itself. The oxygen-free form is constrained by salt-bridges which are broken by the energy of haem–haem interaction with the release of H+. 2,3-Diphosphoglycerate may add to the constraints by being stereochemically complementary to a site between the β-chains ; this complementarity is lost on oxygenation.
2,625 citations
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TL;DR: DPG has a two-fold effect on human deoxyhaemoglobin: it both stabilizes and slightly distorts the S form, and may therefore affect the solubility.
Abstract: DPG has a two-fold effect on human deoxyhaemoglobin. It both stabilizes and slightly distorts the S form, and may therefore affect the solubility.
671 citations
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TL;DR: The structure of sperm whale metmyoglobin has been refined using new intensity data to 2·0 A collected on a four-circle diffractometer starting with the original phase angles determined by isomorphous replacement with heavy atoms.
635 citations
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TL;DR: Comparison of the structures of human and horse deoxyhaemoglobin indicates that significant differences occur only in the region of the amino terminus and the A helix of the β chain: the positions of the centres of mass of the A helices differ by 1·3 A and those ofThe amino terminal valine residue by 4 to 5 A in the two structures, the separation between the A and E helices being greater in human than in horse de oxygenhaemobic structures.
389 citations