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Consider the following naturally occurring forms of Hb. Hbs (sickle-cell Hb): su

ID: 171978 • Letter: C

Question

Consider the following naturally occurring forms of Hb. Hbs (sickle-cell Hb): substitutes a V for a E on the surface Hb Cowtown: eliminates an ion pair involved in T-state stabilization Hb Memphis: substitutes one uncharged polar residue for another of similar size on the surface Hb Bibba: substitutes a P for a L involved in an a helix Hb Milwaukee: substitutes a E for a V Hb Providence: substitutes an N for a K that normally projects into the central cavity of the tetramer Hb Philly: substitutes a F for a Y, disrupting hydrogen bonding at the alpha 1 beta 1 interface of the above, which do you expect to be: A - LEAST least likely to cause pathological symptoms. B - MOST likely to show pl values different from that of HbA on an isoelectric focusing gel C - MOST likely to show a decrease in BPG binding and an increase in the overall affinity of the hemoglobin for oxygen. Explain your answers.

Explanation / Answer

2 A- Hb Memphis has an unconservative substitution, which will not have any effect on the function. So, it is least likely to have any pathological symptom.

2 B- HbS, Hb Milwakee and Hb Providence have substituions which has ultimately changed the net charge on the protein thereby affecting the isoelectric point. Moreover, Hb Cowtown also undergoes a loss of an ion pair which will have an effect on the charge of the protein, but we can not be sure since there is not enough evidence available.

2 C- Hb Providence has an Asparagine residue in place of a Lys residue, which projects in to the central cavity of the protein. Since the Lys is a positively charged residue so losing it causes the affinity towards BPG to reduce and thereby it increases the affinity towards Oxygen.