Sandbox Reserved 426
From Proteopedia
(→Introduction) |
(→Introduction) |
||
| Line 15: | Line 15: | ||
| - | <Structure load='1qxd' size='400' frame='true' align='right' caption='Insert caption here' scene='Insert optional scene name here' /> | + | <Structure load='1qxd' size='400' frame='true' align='right' caption='Insert caption here' scene='Sandbox_Reserved_426/Glu6_residue_of_hb/3<ref></ref>' /> |
| + | |||
| + | <Structure load='1qxd' size='200' frame='true' align='left' caption='Insert caption here' scene='Insert optional scene name here' /> | ||
===Overall Structure=== | ===Overall Structure=== | ||
Revision as of 17:31, 24 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. |
YourMacromolecule
Introduction
Individuals with Sickle Cell Anemia, or Sickle Cell Disease, contain a mutated form of hemoglobin, the oxygen binding protein found in red blood cells. Mutated hemoglobin causes normal disk-shaped red blood cells to become sickle-shaped. These sickle cells are fragile, deliver less oxygen to the body's tissues, and clog small blood vessels and capillaries, which results in a variety of adverse symptoms and detrimental complications. Some of these symptoms include abdominal and bone pain, breathlessness, fatigue, and rapid heart rate. Over time, irreversible tissue damage leads to the failure of many organ systems.
Sickle Cell Disease results from a single point mutation in the Hemoglobin amino acid sequence. Normal Hb contains a hydrophilic glutamate residue at position 6 of the beta strand, whereas in HbS, this residue has been changed to a hydrophobic valine residue. . The mutation region of one HbS molecule will then bind to a region defined by β Phe85 and β Leu88 in the Heme pocket of another HbS molecule via noncovalent hydrophobic interactions. The subsequent polymerization of HbS molecules leads to the sickling of red blood cells.
The cooperative binding of oxygen leads to a conformation change in hemoglobin from the tense, or T state, to the R, or relaxed state. Recently, studies have shown that multiple relaxed Hb conformers exist, such as the R2, RR2, and R3 states.It has been proven that sickling only occurs with the deoxygenated T-state Hb, and it is therefore desirable to explore ways in which allosteric equilibrium can be shifted toward the R- conformation. Compounds that achieve such an equilibrium shift are therefore being sought. Vanillin, a food flavoring compound, as well as the furanic aldehyde compounds 5-hydroxymethyl-2-furfural (5HMF), 5-methyl-2-furfural (5MF), 5-ethyl-furfural (5EF), and furfural (FUF) all exhibit such antisickling properties and are nontoxic to humans, and are therefore promising candidates for potential SCD drug treatments.
| |||||||||||
