lecture0217final - Misfolding can be fatal Sickle cell...

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Mis-folding can be fatal Sickle cell disease is one of the more  common abnormalities of the oxygen- binding protein, haemoglobin (Hb).  The single substitution of non-polar valine  for charged glutamate at one position in  the primary sequence of Hb alters the  folding of the protein and its binding of  oxygen Both “mad-cow” and Alzheimer’s disease  may result from accumulations, “plaques”  of mis-folded proteins in the brain
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HP Figure 1 Normal and abnormal prion proteins implicated  in “mad cow” disease
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Covalent modificactions to proteins 1) Phosphorylation Addition of a negatively CHARGED  phosphate group to the R-group of  serine, threonine, tyrosine (all contain OH)  e.g. serine,              R= -CH 2 -OH,            phosphoserine,   R= -CH 2 -O-PO 3 2-  Phosphate usually comes from ATP,   forming the phospho-amino acid + ADP.  This reaction catalysed by a class of  enzymes known as protein kinases.  Phosphorylation can have profound  structural and functional consequences -
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Covalent modifications to proteins 2) Addition of sugars - Glycosylation - Carbohydrate chains (2-60 sugar  monomers) can be joined to OH  group of serine (O-linked) or NH2  group of asparagine (N-linked).    Glycoproteins. 
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HP Figure 1 N- and )-linkages in glycoproteins Fig. 4.10
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HP Figure 1
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HP Figure 1
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Glycoproteins  The added carbohydrates stabilize  protein structure in aqueous  environments and protect against 
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This note was uploaded on 05/11/2010 for the course BIOLOGY 105 taught by Professor Richard during the Spring '10 term at George Mason.

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lecture0217final - Misfolding can be fatal Sickle cell...

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