Allosteric transition intermediates modelled by crosslinked haemoglobins
| Autor: | Richard T. Jones, Richard G. Brennan, Ronald Kluger, Melinda M. Dixon, Maria A. Schumacher |
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| Rok vydání: | 1995 |
| Předmět: |
Models
Molecular Multidisciplinary Hemeprotein Stereochemistry Protein Conformation Allosteric regulation Oxygen transport chemistry.chemical_element Crystal structure Crystallography X-Ray Oxygen chemistry.chemical_compound Hemoglobins Protein structure Cross-Linking Reagents chemistry Allosteric Regulation Computer Graphics Humans Trimesic acid Carbon monoxide |
| Zdroj: | Nature. 375(6526) |
| ISSN: | 0028-0836 |
| Popis: | The structural end-points of haemoglobin's transition from its low-oxygen-affinity (T) to high-oxygen-affinity (R) state, have been well established by X-ray crystallography, but short-lived intermediates have proved less amenable to X-ray studies. Here we use chemical crosslinking to fix these intermediates for structural characterization. We describe the X-ray structures of three haemoglobins, alpha 2 beta 1S82 beta, alpha 2 beta 1Tm82 beta and alpha 2 beta 1,82Tm82 beta, which were crosslinked between the amino groups of residues beta Val1 and beta Lys82 by 3,3'-stilbenedicarboxylic acid (S) or trimesic acid (Tm) while in the deoxy state, and saturated with carbon monoxide before crystallization. alpha 2 beta 1S82 beta, which has almost normal oxygen affinity, is completely in the R-state conformation; however, alpha 2 beta 1Tm82 beta and alpha 2 beta 1,82Tm82 beta, both of which have low oxygen affinity, have been prevented from completing their transition into the R state and display many features of a transitional intermediate. These haemoglobins therefore represent a snapshot of the nascent R state. |
| Databáze: | OpenAIRE |
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