Searching for protein composition and function

Two components of protein, amino acids leucine and glycine were isolated by Henri Braconnot (1780–1855) in 1819 and 1820.

Gerardus Johannes Mulder (1802-1880) found the proteins to be enormous molecules. Much bigger than 18th-century chemists have seen before. In his paper, published in 1838, On the composition of some animal substances, he described the chemical composition of several proteins and found that all of them have the same composition: C400H620N100O120P1S1.

Mulder suggested that all proteins consist of one primary substance (Grundstoff) and that animals get most of their proteins from plants. He also searched for components of proteins, smaller molecules. He found these molecules to contain both amino and carboxylic acid functions; Consequently, these protein components were named amino acids.

A Swedish chemist and clinician, Jöns Jacob Berzelius (1779-1848) suggested the name protein to Mulder. That was because if proteins were a fundamental substance, then the meaning "primary", "in the lead", or "standing in front" from the Greek word ‘proteios’ was appropriate.

Proteins are composed of amino acids, connected in a chain called polypeptides. In 1902, Franz Hofmeister argued that amino acids are linked together by amide bonds. The term peptide originated from the work of organic chemist Emil Fischer, who introduced his theory of the protein structure at the same meeting in Karlsbad where Hofmeister presented his theory; Hence, the name polypeptide.

In the 1920s T. Svedberg used his ultracentrifuge technique to demonstrate that proteins, in fact, were large molecules, macromolecules. Other scientists were also able to confirm the size range.

James B. Sumner worked over almost nine years isolating proteins from jack bean (Canavalia ensiformis) and managed to purify and crystallize protein urease. In his photographs, the crystals of the proteins had regular three-dimensional structures. Sumner also presented evidence in his 1926 paper, that urease is an enzyme, which was controversial at the time. Scientists widely believed that a coenzyme of urease exists.

Sumner shared the 1946 Nobel Prize in Chemistry, "for his discovery that enzymes can be crystallized." with John Howard Northrop and Wendell Meredith Stanley, "for their preparation of enzymes and virus proteins in a pure form."

Nikolai Koltsov a Russian biologist proposed in 1927 that genetic information was in proteins as a code, residing in amino acid chains. A giant hereditary molecule could mediate the inheritance of traits. This molecule consists of two,"mirror strands that would replicate in a semi-conservative fashion using each strand as a template."

Over the years scientists found an increasing number of amino acids. The list of 20 amino acids was completed when William Rose in 1935 identified threonine(*). In fact, there are two additional ones, selenocysteine and pyrrolysine, but we’ll come back to this later.

In his 1940 paper A Theory of the Structure and Process of Formation of Antibodies, Linus Pauling proposed that it is the three-dimensional structure of polypeptides, that dictates their specificity.

Insulin, a protein, and a hormone that regulates sugar content in blood was the first one to be sequenced. Between 1949 and 1952, Frederick Sanger determined the amino acid sequence of both A and B chains of the insulin molecule from an ox. For this achievement, Sanger won the Nobel Prize in 1958. Sanger received yet another Nobel Prize in 1980, but more about that later.