Question

Consider the following naturally occurring forms of Hb. A. HbS (sickle-cell Hb): substitutes a V for a E on the surface B. Hb Cowtown: eliminates an ion pair involved in T-state stabilization C. Hb Memphis: substitutes one uncharged polar residue for another of similar size on the surface D. Hb Bibba: substitutes a P for a L involved in an a helix E. Hb Milwaukee: substitutes a E for a V F. Hb Providence: substitutes an N for a K that normally projects into the central cavity of the tetramer Of the above, which do you expect to be: LEAST likely to cause pathological symptoms. MOST likely to show pI values different from that of HbA on an isoelectric focusing gel. MOST likely to show an increase in the overall affinity of the hemoglobin for oxygen. EXPLAIN your answers.

Answer 1

Answer:

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.

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.

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.

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