Sandbox Reserved 426
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===Introduction=== | ===Introduction=== | ||
| - | Sickle Cell Disease (SCD) is the result of a single point mutation in Hemoglobin | + | Hemoglobin, or Hb, is a tetramer composed of two alpha beta dimers |
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| + | The deoxy conformation of Hb is known as the T state, where as that bound to oxygen is the R state | ||
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| + | Structural tension of T state attributed to interdimer salt bridges and hydrogen bonds, and the binding of 2,3-biphosphoglycerate (BPG) | ||
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| + | Oxygen binding induces a transition from the T to the R state, which disrupts the interdimer interactions, and results in the expulsion of BPG. The alpha1beta1 dimer rotates 12-15 degrees with respect to the alpha2beta2 dimer | ||
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| + | Sickle Cell Disease (SCD) is the result of a single point mutation in Hemoglobin, in which Beta Glu6 is replaced by Beta Val6. This leads to hydrophobic contacts between the mutation region of one HbS molecule and a region defined by beta Phe85 and beta Leu88 in the heme pocket of another HbS molecule. This occurs only in the T state, and causes polymerization of T state molecules. | ||
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| + | Red blood cells containing these polymerized HbS T-state molecules become sickle-shaped. These sickle-shaped cells block small capilaries, cause severe pain, and lead to tissue damage. | ||
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| + | Oxygenated HbS does not form polymers, and it is therefore desirable to regulate allosteric equilibrium in favor of the R conformation. Compounds that can cause this allosteric shift are therefore being sought. Aldehydes that form Schiff base adducts with Hb, including Vanillin and 5HMF, are potentially promising candidates for sickle cell treatment. | ||
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| - | Beta Glu6 is replaced by Beta Val6 | ||
Revision as of 17:18, 4 March 2012
| This Sandbox is Reserved from January 19, 2016, through August 31, 2016 for use for Proteopedia Team Projects by the class Chemistry 423 Biochemistry for Chemists taught by Lynmarie K Thompson at University of Massachusetts Amherst, USA. This reservation includes Sandbox Reserved 425 through Sandbox Reserved 439. |
Contents |
YourMacromolecule
Introduction
Hemoglobin, or Hb, is a tetramer composed of two alpha beta dimers
The deoxy conformation of Hb is known as the T state, where as that bound to oxygen is the R state
Structural tension of T state attributed to interdimer salt bridges and hydrogen bonds, and the binding of 2,3-biphosphoglycerate (BPG)
Oxygen binding induces a transition from the T to the R state, which disrupts the interdimer interactions, and results in the expulsion of BPG. The alpha1beta1 dimer rotates 12-15 degrees with respect to the alpha2beta2 dimer
Sickle Cell Disease (SCD) is the result of a single point mutation in Hemoglobin, in which Beta Glu6 is replaced by Beta Val6. This leads to hydrophobic contacts between the mutation region of one HbS molecule and a region defined by beta Phe85 and beta Leu88 in the heme pocket of another HbS molecule. This occurs only in the T state, and causes polymerization of T state molecules.
Red blood cells containing these polymerized HbS T-state molecules become sickle-shaped. These sickle-shaped cells block small capilaries, cause severe pain, and lead to tissue damage.
Oxygenated HbS does not form polymers, and it is therefore desirable to regulate allosteric equilibrium in favor of the R conformation. Compounds that can cause this allosteric shift are therefore being sought. Aldehydes that form Schiff base adducts with Hb, including Vanillin and 5HMF, are potentially promising candidates for sickle cell treatment.
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Binding Interactions
Additional Features
Credits
Introduction - Ryan Colombo
Overall Structure - name of team member
Drug Binding Site - name of team member
Additional Features - name of team member
