Researchers Are Devising New Protein Catalysts
 hat
if you needed a protein that would catalyze a chemical reaction of your own choosing-perhaps
a reaction not normally found in nature or a reaction that takes place, but very
slowly? Could you use the available database of molecular structures to choose and
alter an existing protein to do the job? University researchers are seeking answers
to these questions and taking the first steps toward devising new protein catalysts
by altering certain proteins so that they function as enzymes. Enzymes are a special
form of biological macromolecule that catalyze biochemical reactions with very high
selective properties and turnover rates. Highly selective reactions discriminate
between structurally close, but not identical, reactants. Turnover rate is defined
as the number of reactant molecules that are changed per minute per enzyme molecule.
The researchers are investigating the possibility of using proteins as frameworks
for the design and testing of molecular apparatuses that can catalyze new chemical
reactions-an area of research that combines the principles of chemistry, structural
biology, and the computational sciences. Two groups at the University of Minnesota
are collaboratively constructing new catalysts using the framework of a protein molecule
that is normally involved in fat metabolism and has no enzymatic activity of its
own. The molecular structure of this protein (Adipocyte Lipid Binding Protein, or
ALBP) is shown in the accompanying figure. Professor Mark Distefano in the Department
of Chemistry and his colleagues Hao Kuang, Ron Davies, and Aram Mazhary have chemically
altered ALBP by attaching extra atoms which would catalyze a reaction involving the
production of a keto acid from an amino acid. This work was first put to the test
by observing whether the products of the reaction were mainly of one conformation,
or stereoisomer. Stereoselectivity was seen, offering evidence that a chemical reaction
had occurred and that ALBP may, indeed, be functioning as an enzyme. Establishing
this stereoselectivity is the first step in devising new protein catalysts. |
 |
| Chemically altered molecular structure of
Adipocyte Lipid Binding Protein |
Next, Jeramia Ory, a graduate student in the laboratory of Professor Len Banaszak
in the Medical School's Department of Biochemistry, determined the crystal structures
of the modified proteins. One of the "new" proteins can be seen in the
accompanying figure.
Determining the crystal structures in subsequent studies required the use of the
computational resources at the Supercomputing Institute. When knowledge of the positions
of most of the atoms in the modified protein is obtained from the crystallographic
coordinates, an attempt can be made to analyze the source of the stereoselectivity
and to redesign the protein to improve its catalytic properties or turnover rate.
The figure on page one shows a ribbon diagram of the structure of the modified ALBP
molecule with the extra atoms, a pyridoxamine group, shown as ball and sticks. Notice
how the pyridoxamine is totally surrounded by the protein. The results show that
the protein framework only allows molecules access to the pyridoxamine from one side. |
|
|
This information is available in alternative formats upon request by
individuals with disabilities. Please send email to
alt-format@msi.umn.edu
or call 612-624-0528.
|
|
URL: http://
|
|
|
This page last modified on
|
|
Website related questions or problems should be directed to
webmaster@msi.umn.edu
The Supercomputing Institute does not collect personal information on
visitors to our website. For the University of Minnesota policy, see
www.privacy.umn.edu.
|
|
| |
