William Howard Stein
(1911 - 1980)
William Howard Stein was born on June 25, 1911, in
New York City. Both of his parents were very active in local public
affairs and persuaded William to study medicine. Stein graduated from
Harvard in 1933, majoring in chemistry, and decided to continue his
graduate studies at Harvard. After a year, however, Stein transferred
to the Department of Biochemistry at Columbia University in New York
City.
In 1937, after completing his schooling, Stein went
to the Rockefeller Institute for Medical Research in the laboratory
of Max Bergmann. Stein considered Bergmann one of the greatest protein
chemists of the century. It was during this time, that Stein and collaborator
Stanford Moore began studying the amino acid composition of proteins.
They devised a way to separate amino acids using the proper form of
potato starch. It was from such analysis that these men began their
research on the amino acid structure of ribonuclease. (Ribonuclease
is an enzyme/protein that accelerates the reaction rate of the breakdown
of RNA into smaller components. RNA copies genetic information from
DNA and then translates it into proteins for the body to use). After
years of dedicated research, Stein was promoted to professorship at
the Institute in 1954.
Stein was a member of several privileged scientific
societies including the National Academy of Science, American Chemical
Society, and the American Association for the Advancement of Science.
From 1958-1961, he was the Chairman of the Editorial Committee of the
Journal of Biological Chemistry and elected Editor from 1968-1971, when
he retired from illness.
William Stein received the Nobel
Prize for Chemistry in 1972 along with Christian Boehmer Anfinsen
and Stanford Moore for their research involving ribonuclease. These
men furthered the world’s understanding of the chemical and amino
acid structure of the molecular enzyme ribonuclease.
Stein died on February 2, 1980, in his beloved city
of New York.
The following press release
from the Royal Swedish Academy of Sciences
describes Stein's work:
This year's Nobel Prize in Chemistry has been awarded
to three scientists who have made fundamental contributions to enzyme
chemistry. They have worked with the same enzyme, ribonuclease. Anfinsen's
investigations have provided the answer to an important question concerning
the way in which the active enzyme is formed in living cells. Moore
and Stein have elucidated important principles related to the biological
activity of the enzyme.
Those properties we generally
associate with the concept of life and
with living organisms - such as reproductive
ability, growth, motility and reaction
to external stimuli - are nothing but outward
manifestations of a very complicated network
of coupled chemical reactions. The chemical
reactions in living cells are accelerated
(catalyzed) by specific proteins, called
enzymes. Consequently, enzymes must in
many respects be considered the key substances
of life. This becomes rather obvious from
consideration based on the most important
results of biochemical genetics, summarized
in "the central dogma of molecular biology":
DNA --> RNA --> enzyme
DNA (deoxyribonucleic acid) is the carrier of the traits
of inheritance, and these become expressed by DNA controlling the synthesis
of enzymes.
Like all proteins enzymes are built up from about 20
different amino acids, which are linked together in long chains through
peptide bonds. The existence of several thousand enzymes with very different
specific properties, despite these similarities in structure, depends
on differences in the number and sequence of amino acids between the
molecules of different proteins. We now know that the genetic information
in the DNA of a cell nucleus is indeed used to determine the sequence
of the amino acid residues making up the peptide chain. An active enzyme
is, however, not a long string of amino acids joined together through
peptide bonds, but the chain is in general folded into a globular (ball-like)
shape. In principle, it is of course possible to fold a given chain
in many ways but it has been shown that the active enzyme has a singular
unique three-dimensional structure (conformation). An important question,
is the source of the information required for the peptide chain of a
given enzyme to assume its specific confromation. In investigations
on the enzyme ribonuclease Anfinsen has shown that this information
is inherent in the linear sequence of amino acid residues in the peptide
chain, so that no further genetic information than that found in DNA
is needed. The driving force is the tendency of each system to assume
a state of minimum energy. More precisely this can be expressed by saying
that the conformation of the enzyme represents the thermodynamically
most stable state in the intracellular environment.
The enzymes are large molecules (macromolecules). The
way in which an enzyme accelerates a chemical reaction involves an interaction
of the reacting substance (the substrate) with only a limited part of
the enzyme molecule, its active site. Anfinsen, Moore and Stein have
carried out investigations which supplement each other and have led
to a complete elucidation of the sequence of amino acids in the enzyme
ribonuclease. It soon became obvious, however, that this knowledge alone
tells us very little about the structure of the active site. The three-dimensional
structure may bring together in the active site groups which are far
apart in the linear sequence. Moore and Stein however, made an observation
with ribonuclease of great general significance, namely that groups
in the active site often have an anomalously high reactivity. This increased
reactivity was utilized by Moore and Stein for chemical modification
of groups in the active site, and in this way the position of these
groups in the sequence could be unambiguously determined. Through these
investigations Moore and Stein could give a detailed picture of the
active site of ribonuclease long before the three-dimensional structure
of the enzyme had been determined.
In summary it may be said that Anfinsen, Moore and
Stein in pioneering studies have illuminated some of the most important
principles describing the relation between the chemical structure and
catalytic activity of an enzyme.
Sources: Wikipedia;
"William
Howard Stein Autobiography"; Britannica;
press release: "The
1972 Nobel Prize in Chemistry" |