Structure of Proinsulin and Protein Malfunction

Vocabulary flashcards covering the enzymatic conversion of proinsulin to insulin, amino acid interactions, structural mutations, and their link to type one diabetes.

Proinsulin

A protein substrate that is cleaved by enzymes such as trypsin to produce insulin and peptide C.

Trypsin

An enzyme that catalyzes the conversion of proinsulin to insulin by cleaving peptide bonds involving arginine at two specific sites.

Peptide C

One of the two smaller peptides produced, along with insulin, when trypsin breaks peptide bonds in proinsulin.

Insulin

A peptide hormone produced from the cleavage of proinsulin that regulates the concentration of glucose in the blood.

Serine (in trypsin)

An amino acid located in the active site of trypsin whose terminal R group oxygen ionizes to form a negatively charged anion, attracting positively charged arginine.

Arginine (in proinsulin)

An amino acid with a positively charged R group that ionically bonds to the active site of trypsin, allowing proinsulin to be cleaved.

Cysteine

An amino acid containing an uncharged sulfur R group that forms covalent disulfide bonds linking secondary structures to establish tertiary structure.

Disulfide bond

A covalent bond formed between the R groups of cysteine molecules that links secondary structures together to form tertiary structure.

Tyrosine

An amino acid with an R group composed of a large nonpolar ring of carbon and hydrogen atoms that folds toward the interior of the protein.

Arginine-to-cysteine substitution

A mutation in proinsulin that alters the R group from positively charged to an uncharged sulfur group, abolishing ionic binding to trypsin and reducing binding to $\frac{1}{10}$ of its typical amount.

Cysteine-to-tyrosine substitution

A mutation in proinsulin preventing disulfide bond formation, causing inward folding toward nonpolar residues and reducing proinsulin binding to $\frac{1}{10}$ of its typical amount.

Type one diabetes

A disease that can result from a single amino acid change in proinsulin, preventing its conversion to insulin and leading to insufficient regulation of blood glucose concentration.