(Biochemistry) For each of the Hb mutants below, determine how the mutation woul

Question

(Biochemistry)

For each of the Hb mutants below, determine how the mutation would alter O2 binding relative to wild type Hb. In each case the wild type amino acid is on the left of the arrow and the mutant is on the right (wild typeàmutant).

Relative to wild type Hb, the mutant would be more T or R favored; demonstrate a hyperbolic or sigmoidal binding curve; have an increased or decreased p50 value.

1. Hb Zurich: His146 -> Arg: A His residue (pKR 6) responsible for Bohr proton binding is mutated to an Arg (pKR 12).   Relative to wild type Hb, the mutant would be more…

A) T; sigmoidal, decreased

B) R; hyperbolic, decreased

C) R, sigmoidal, increased

D) T, sigmoidal, increased

E) R, sigmoidal, decreased

2. Hb Toms River: Val -> Met: A Val in the O2 binding pocket mutated to Met making ligand binding pocket less nonpolar (more polar). Relative to wild type Hb, the mutant would be more…

A) T; sigmoidal, decreased

B) R; hyperbolic, decreased

C) R, sigmoidal, increased

D) T, sigmoidal, increased

E) R, sigmoidal, decreased

3. Hb Beth Israel: Asn -> Ser: An Asn at the subunit interface is mutated to a Ser leading to a 15 kJ/mol increase in the energy of the oxygenated R state compared to the oxygenated T state. Relative to wild type Hb, the mutant would be more…

A) T; sigmoidal, decreased

B) R; hyperbolic, decreased

C) R, sigmoidal, increased

D) T, sigmoidal, increased

E) R, sigmoidal, decreased

4. Hb Helsinki Lys -> Met: A Lys pointing into the central cavity of the Hb tetramer is replaced with a Met. Relative to wild type Hb, the mutant would be more…

A) T; sigmoidal, decreased

B) R; hyperbolic, decreased

C) R, sigmoidal, increased

D) T, sigmoidal, increased

E) R, sigmoidal, decreased

5. Hb Kempsey: Asp -> Asn: Experimental data show Hb Kempsey has “ a p50 at pH 7.2 was 10% that of wild type Hb. At pH 6.8 and 6.0, the p50 value did not significantly differ from wild type Hb.” Relative to wild type Hb, the mutant would be more…

A) T; sigmoidal, decreased

B) R; hyperbolic, decreased

C) R, sigmoidal, increased

D) T, sigmoidal, increased

E) R, sigmoidal, decreased

Explanation / Answer

Answer1-

Histidine and arginine both are positively charged amino acids. Therefore, mutation from His to Arg does not make a great change in activity of hemoglobin. Histidine codes by CAT and CAC codons while Arginine by CGT and CGC therefore, mutation can do in A to G form that is R favored. The curve will be hyperbolic because the binding affinity will reduce after such mutation. Therefore, the correct option is B.

Note- non-conservative mutations will bring loss of function in binding of O2 with Hemoglobin.

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