DEVELOPING AND DESIGNING NEW CHEMICALS AND MATERIALS - Chemistry: Notable Research and Discoveries - page 27

enzymes are proteins that speed up specific chemical reactions in the
body by binding and positioning the reactants. The shape of the reac-
tants fit with the shape and structure of the enzyme, giving the enzyme
its specificity.
Structure-based drug design makes use of the data from X-ray crys-
tallography and NMR techniques. If the biology of the disease process
is understood well enough to identify an important component, then
researchers can search for a molecule having a structure that might be
able to affect this component. For example, protein kinases are a family
of enzymes that are involved in many of the functions of a cell. Disrup-
tions of these enzymes have been associated with a significant number
of diseases, such as breast cancer, and this makes protein kinases an im-
portant target for drug development. For this development to succeed,
the structure of protein kinases must be studied.
Proteins are composed of a string of amino acids, the sequence of
which governs the proteins' properties. In the family of protein kinases,
the members share certain sequences—these sequences are “conserved,”
presumably because they are critical in the function of all protein ki-
nases—and other sequences vary, which provides the specificity of the
individual enzymes. Drug designers must identify these sequences and
understand their role. In 2007, James D. R. Knight and Rashmi Kothary
of the University of Ottawa in Canada, along with Bin Qian and David
Baker of the University of Washington in Seattle, accomplished one step
in this process by publishing an analysis of protein kinase structures.
The paper, “Conservation, Variability and the Modeling of Active Pro-
tein Kinases,” published in Public Library of Science (PLoS) ONE, com-
pared some of the 518 known human protein kinases and introduced
an algorithm that may become useful in predicting their structures.
Antibiotics is another area in need of drug development. Although
many antibiotics have been developed, microorganisms evolve rapidly.
Some of the mutations give microorganisms protection against certain
antibiotics, which has caused dangerous and sometimes fatal antibiotic-
resistant infections. Ray Zarivach and Natalie Strynadka, at the Univer-
sity of British Columbia in Canada, and their colleagues are studying a
number of proteins used by certain bacteria to invade and attack their
host. For example, a group of interacting proteins known as the type III
secretion system is involved in the injection of bacterial molecules into
human cells, which often leads to disease. By studying the structure of