work published in Science
Professor Debra Dunaway-Mariano and graduate student Guofeng
Zhang teamed with Boston University School of Medicine researchers
to get the first glimpse of a chemical reaction as it is in
the process of transforming to the chemical product.
crystallographic methods to take a snap shot of the molecule
in its state of transition, the researchers provided unequivocal
proof for the existence of a long sought after chemical intermediate
in phosphoryl transfer processes.
recently featured in Science magazine, was so significant that
it was treated as a Science Express paper meaning that independent
of the field of science, the editors at Science magazine give
their full attention to the paper and expedite the publishing
process. A paper classified as such is sent out for review within
two weeks and subsequently placed on the Internet. Between the
time the paper is submitted and the availability to the public
is approximately four weeks.
really gave this article special attention, said Dunaway-Mariano.
That shows right there that this has big impact. It was
an important finding. Its out there in terms of recognition.
One of the reasons why it was very important is because it is
in the area of basic research. Often breakthroughs in basic
research have long reaching effects in the applied sciences.
For instance, the structure of the phosphorane intermediate
will no doubt become the center of focus in drug design targeting
phosphoryl transfer enzymes. Pharmaceutical companies develop
new drugs based on structural mimicry, and phosphoryl transfer
enzymes are the hottest of the hot new drug targets.
luck is how Dunaway-Mariano explained the finding.
were in the process of studying a biological phosphoryl reaction
as it occurred in the presence of its natural protein catalyst,
said Dunaway-Mariano. Protein catalysts, or enzymes, function
in our bodies to speed up reactions. The enzyme closed (like
a clam) over its chemical reactant, forcing it to a state of
transition. We crystallized the molecular complex in this state,
determined its structure and were surprised to find the pentacovalent
phosphorane intermediate, which eluded chemists for five decades.
said reactions that occur in biological systems always require
enzymes to serve as catalyst. There are no chemical reactions
in the human body that occur spontaneously. The presence or
absence of the enzyme determines whether the reaction is turned
on or off. Basically, the human body is the organization of
chemical reactions. These reactions must be very carefully controlled
and timed. Medicines digested act on the enzymes that control
the chemical reactions in our bodies or in our pathogens.
provide chemical reactants a deep crevice in which they can
bind, Dunaway-Mariano said. The enzyme closes the
entrance and squeezes down on the reactant. The enzyme relaxes
once the product is formed so that it can swim away. Where we
got lucky was that our enzyme formed crystals only from the
closed state. The molecules were so tightly packed in the crystal
that the enzyme could not open. In this closed state the phosphorane
intermediate, a chemical species which is half-way between reactant
and product, was frozen in time. In solution this phosphorane
would be gone in less than a second. In the crystal it lasts
involved in the research include Karen Allen, associate professor,
and Sushmita Lahiri, graduate student, both of Boston University.
the research was that to take a picture, something had to stand
still in time. The luck part in this process was the fact
that the species we were looking for was trapped inside a crystal,
Dunaway-Mariano said. This made it stable in time. As
long as it was trapped inside this crystal, you could take pictures
of it. Most reactions occur in a solution or some type of a
of the pentacovalent phosphorane species addresses a question
that chemists have been fighting over for more than 50 years,
there is a definitive result, Dunaway-Mariano said. We
know now that phosphoryl transfer reactions take place through
a pentacovalent phosphorane intermediate. It was extremely pleasing
for scientists to actually see this intermediate following decades
of arguing back and forth as to its existence while trying every
experiment that they could think of to prove their position.
a chemistry concept that had been the subject of debate for
at least half a century. And then, all of a sudden theres
a definitive picture (an actual photograph) of the species people
have been arguing about. Its something everybody wanted
to see, but never got the chance to see it.
came to UNM after 18 years of university service in the Washington
D.C. area. Its very pleasant here, my students and
colleagues are wonderful and these are the essential ingredients
of good science, she said.
says people should expect to see more great research coming
out of the chemistry department at UNM and the enzyme catalyzed
reaction trapping is an example.