Question 73:
In 1953, Frederick Sanger determined the amino acid sequence of which protein?
Catalase has the highest turnover number among these enzymes, but Frederick Sanger determined the amino acid sequence of insulin in 1953, revolutionizing protein biochemistry. This was the first complete protein sequence ever achieved.
Correct Answer
(C) Insulin
Historical Context
Frederick Sanger’s 1953 work (published 1951-1955) sequenced insulin’s A-chain (21 amino acids) and B-chain (30 amino acids), proving proteins have precise, genetically determined sequences. Using Sanger’s reagent (FDNB), partial hydrolysis, chromatography, and electrophoresis, he mapped all 51 residues and disulfide bonds—earning the 1958 Nobel Prize.
Option Analysis
| Option | Enzyme/Protein | Status | Explanation |
|---|---|---|---|
| (A) Caspase | Apoptosis protease | Wrong | Discovered 1989s; no 1953 connection. |
| (B) Hemoglobin | Oxygen carrier | Wrong | Sequenced 1950s-60s (Ingram, 1957); post-Sanger. |
| (C) Insulin | Hormone | Correct | Sanger’s 1951-55 work; first complete protein sequence. |
| (D) DNA polymerase | DNA synthesis | Wrong | Protein identified 1950s; sequenced much later. |
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(A) Caspase: Programmed cell death enzymes; unknown in 1953.
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(B) Hemoglobin: Partial sequencing began after insulin; full human α/β chains came later.
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**(C) Correct: Sanger’s insulin work (bovine A/B chains) established protein sequencing field.
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(D) DNA polymerase: Arthur Kornberg purified first (1956); sequencing decades later.
Why Insulin Was Chosen
Small size (51 aa), clinical relevance (diabetes), and availability made insulin ideal. Sanger proved proteins aren’t random colloids but have defined primary structure—foundation for genetic code hypothesis.
Frederick Sanger 1953 amino acid sequence determination of insulin marked the birth of protein biochemistry. This GATE Life Sciences classic tests historical milestones in molecular biology.
Sanger’s Insulin Breakthrough Timeline
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1945: Identified N-terminal residues (Gly, Phe) using FDNB reagent
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1951: B-chain (30 aa: FVNQHLCGSHLVEALYLVCGERGFFYTPKT) complete
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1953: A-chain (21 aa: GIVEQCCTSICSLYQLENYCN) complete
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1955: Disulfide bonds mapped (2 interchain, 1 intrachain)
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1958: Nobel Prize in Chemistry
Sanger used partial hydrolysis (acid/enzymatic), 2D chromatography/electrophoresis (“fingerprints”), and end-group analysis to assemble overlapping peptides.
Complete Bovine Insulin Sequence
A-chain: GIVEQCCTSICSLYQLENYCN (21 residues)
B-chain: FVNQHLCGSHLVEALYLVCGERGFFYTPKT (30 residues)
Disulfides: A7-B7, A20-B19, A6-A11
Why Not Other Options?
| Protein | Discovery/Sequencing | Why Wrong |
|---|---|---|
| Caspase | 1989s | Doesn’t exist in 1953 |
| Hemoglobin | 1957 (Ingram) | After Sanger’s insulin |
| DNA pol | 1956 (Kornberg) | Function known later |
Frederick Sanger 1953 amino acid sequence work proved “one gene-one polypeptide” hypothesis foundation. Insulin’s two chains linked by cysteines showed protein complexity.
GATE Exam Strategy
Expect: “Frederick Sanger determined sequence of which protein?” Always insulin. Distinguish from DNA sequencing (Sanger’s 2nd Nobel, 1980). Remember: 1953 = insulin, proteins.
Technique Innovation
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Sanger’s reagent (FDNB): Labels N-termini yellow
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Partial hydrolysis: Creates overlapping peptides
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Fingerprinting: 2D separation (electrophoresis × chromatography)
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Sequence assembly: Overlap reconstruction
This Frederick Sanger 1953 amino acid sequence methodology enabled modern proteomics. Master for biochemistry history questions!
