The document discusses the historical understanding and research of proteins, tracing back to ancient times with observations on egg whites and curdled milk. It highlights key developments in protein science, including the discovery of amino acids, the establishment of the peptide bond, and advancements in structural biology techniques such as x-ray crystallography and cryo-electron microscopy. By 2006, the protein data bank had amassed nearly 40,000 atomic-resolution structures, showcasing significant progress in our understanding of protein structures.

2. • The similarity between the cooking of egg
whites and the curdling of milk was
recognized even in ancient times; for example,
the name albumen for the egg-white protein
was coined by Pliny the Elder (a scholar from
ancient Rome) from the Latin albus ovi (egg
white).

3. Ancient people new much about the
similarity of egg white and curdled milk

4. • There had been the concept of an "animal
substance," slight variants of which were thought to
make up muscles, skin, and blood.
• But it turned into hard, hornlike material when
heated and became foul-smelling when kept under
moist, warm conditions, giving off an alkaline vapor.
• This contrasted with the properties of starch and
sugar.
• In 1728, the Italian scholar Jacopo Beccari
announced that he had discovered the presence of
a material with all the characteristics of "animal
substance" in white wheat flour.

5. • Proteins were recognized as a distinct class of
biological molecules by Antoine Fourcroy at
1789
• Members of this class were called albuminoids
• Well-known examples at the start of the
nineteenth century included albumen from egg
whites, blood serum albumin, fibrin, and wheat
gluten

6. • Dutch chemist Gerhardus Johannes Mulder carried
out elemental analyses of common animal and
plant proteins in 1837
• To everyone's surprise, all proteins had nearly the
same empirical formula, roughly C400H620N100O120
with individual sulfur and phosphorus atoms.
• He hypothesized that there was one basic
substance (Grundstoff) of proteins, and that it was
synthesized by plants and absorbed from them by
animals in digestion.

7. • Berzelius supported the theory of Mudler.
• He proposed the name "protein" for this
substance in a letter dated 10 July 1838.
• He said: The name protein that I propose for
the organic oxide of fibrin and albumin, I
wanted to derive from the Greek word
πρωτειος (first; foremost), because it appears
to be the primitive or principal substance of
animal nutrition.

8. Gerardus Johannes Mulder
(1802-1880)
Jöns Jacob Berzelius
(1779-1848)

9. • 1819: Leucine is the first amino acid isolated. The
20th, threonine, was not discovered until 1936.
• 1902: Emil Fisher and Franz Hofmeister
(independently) discover the peptide bond.
• 1907-8: Committees in England and the USA
standardise the term protein.
• 1920: Hermann Staudinger was the first effective
proponent of the idea that true molecules of huge
size are capable of stable existence.
• 1925: N. Bjerrum, E. Q. Adams, K. Linderstrøm-Lang
and others reach consensus about the zwitterionic
character of proteins at the isoelectric pH.

10. • 1929, Hsien Wu hypothesized that denaturation
was protein unfolding, a purely conformational
change that resulted in the exposure of amino acid
side chains to the solvent.
• 1930-1950, The hypothesis of protein folding was
followed by research into the physical interactions
that stabilize folded protein structures.
• The secondary and low-resolution tertiary structure
of globular proteins was investigated initially by
hydrodynamic methods. After 1950, Spectroscopic
methods to probe protein structure were
developed.

11. • The first atomic-resolution structures of proteins
were solved by X-ray crystallography in the 1960s
and by NMR in the 1980s.
• As of 2006, the Protein Data Bank has nearly
40,000 atomic-resolution structures of proteins.
• In more recent times, cryo-electron microscopy of
large macromolecular assemblies and
computational protein structure prediction of
small protein domains are two methods
approaching atomic resolution.