Q.1 Protein P becomes functional upon phosphorylation of a serine residue. Replacing this serine with will result in a phosphomimic mutant of P.
(A) alanine
(B) aspartic acid
(C) phenylalanine
(D) lysine
Aspartic acid replacement creates a phosphomimic mutant by mimicking the negative charge of phosphorylated serine. This is the correct choice for option (B).
Question Breakdown
Protein P requires phosphorylation on a serine (Ser, S) residue to become functional, adding a negatively charged phosphate group (pSer). A phosphomimic mutant substitutes Ser with an amino acid that structurally and electrostatically resembles pSer, locking the protein in an active-like state without needing phosphorylation.
Option Analysis
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(A) Alanine: Neutral, small, non-polar side chain (-CH3). Lacks charge or size to mimic phosphate; creates a non-phosphorylatable dead mutant.
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(B) Aspartic acid: Negatively charged side chain (-CH2-COO-) at physiological pH. Closely mimics pSer’s charge and size, acting as a phosphomimic to maintain function.
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(C) Phenylalanine: Large, hydrophobic aromatic ring. No charge resemblance; disrupts phosphorylation site without mimicking activation.
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(D) Lysine: Positively charged side chain (-(CH2)4-NH3+). Introduces opposite charge, mimicking phospho-inhibition rather than activation.
Protein phosphorylation activates many proteins by adding a phosphate to serine residues, altering charge and conformation. A phosphomimic mutant replaces this serine with aspartic acid (D) to mimic the phosphorylated state (pSer), enabling studies of downstream effects without kinases.
Why Aspartic Acid as Phosphomimic?
Aspartic acid’s carboxylate group (-COO-) carries a negative charge like phosphate, with similar size for steric fit. This substitution (S-to-D) keeps the protein “on” constitutively, ideal for research.
Evaluating Alternatives
| Option | Amino Acid Properties | Effect on Phosphomimic |
|---|---|---|
| Alanine (A) | Neutral, hydrophobic | Blocks phosphorylation; no charge mimic |
| Aspartic acid (B) | Acidic, negative charge | True phosphomimic; activates like pSer |
| Phenylalanine (C) | Aromatic, hydrophobic | No charge; alters structure unrelatedly |
| Lysine (D) | Basic, positive charge | Phospho-null or inhibitory mimic |
Applications in Research
Common in molecular biology for signaling pathways (e.g., MAPK). S-to-A pairs as phospho-dead control. For IIT JAM/GATE prep, recognize Asp as the charge-mimicking choice.
