Please help! I\'m not sure. A type of muscular dystrophy, called severe childhoo
ID: 1076157 • Letter: P
Question
Please help! I'm not sure.
A type of muscular dystrophy, called severe childhood autosomal recessive muscular dystrophy (SCARMD), results from a mutation in the gene for a 50-kD muscle protein. The defective protein leads to muscle necrosis. Detailed studies of this protein have revealed that an arginine residue at position 98 is mutated to a histidine. Which of the answers below are plausible explanations for this? [ The difference in the pK values of Arg and His are sufficiently different to indicate that although Arg is likely to be positively charged under localized conditions of pH, His might not be Only Arg can form ion pairs. The straight chain structure of the Arg side chain vs. the ring structure of His side chain. Only Arg can hydrogen bondExplanation / Answer
Ans. Option 1. True. Arginine (pKc = 12.1) bears a +1.0 unit positive charge at physiological pH of 7.2 whereas Histidine (pKc = 6.04) bears only +0.065 unit charge at same pH – use Henderson-Hasselbalch equation for base to calculate charge on the side chain. Therefore, the mutation leads to the conversion of a positively charged residue (Arg, +1.0 unit charge) into an almost neutral residue (His, +0.065 unit charge). The alteration is charge may cause the mutated His residue not participate ionic residue with adjacent negatively charged residues or any other negatively charged moieties that interacted normally with positively charged Arg residue.
# Option 2: True. As explained above, the mutated His can’t participate ionic interaction (or form ion pair) with a negatively charged residue because it’s almost neutral. Whereas, Arg can form ion pair with a negatively charged residue because it’s positively charged.
#Option 3. True. Arginine has a bulky, straight side chain whereas that of His is cyclic. Since correct 3D configuration of all atoms is crucial for optimal inter- and intramolecular interaction of a molecule, the change is chain structure due to mutation (linear in Arg vs cyclic in His) is most likely to disrupt the normal thermodynamic stability of the protein.
Option 4. False. Hydrogen bond is a weak attractive force between a highly electronegative atoms (O, N, F) and a H-atoms linked to such atoms.
The criteria for H-bonds formation is that there must be -
I. A highly electronegative atom (F, N, O-atom), and
II. A H-atoms linked to such atoms (F, N, O).
His can form H-bonds through its N-atoms in the ring (side chain) as well as the N-linked H-atom in the ring, too.
Arg can also form H-bonds with its O-atoms, N-atom and H-atoms liked to an O- or N-atom in the side chain.
Therefore, both His and Arg can form H-bonds.
# So, correct options are- 1, 2, 3.