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This is important because drugs seek to bind,
or dock, to target enzymes in the infrequent high-energy state. Kern
believes the study brings scientists a step closer to a new area of
research that seeks to elucidate the structures of enzymes in
high-energy states that can be ultimately used for rational drug
design.
"This research shifts the paradigm of how we thought proteins work.
The traditional view is that proteins are not terribly dynamic when
they do not perform their function, and that they become dynamic only
during catalysis, their active state. What we have learned now is that
there is no resting state, that even in the absence of substrates,
before catalysis, defined motions of many atoms is an intrinsic
property of these enzymes," explained Kern.
"Much like a rousing basketball game – in which all the players
continuously but strategically move with or without the ball – nature
has evolved these biomolecules so that they are constantly moving in
highly-defined directions conducive to their function with or without
the substrate," explained Kern, who played for the East German
National basketball team before the Berlin Wall fell in 1989 and later
professional basketball for united Germany.
The research involved NMR studies of the enzyme cyclophilin A, a
highly conserved protein found in all organisms from yeast to the
human body, and which is involved in HIV replication in humans.
Elucidating the role that cyclophilin A plays in the body would be a
major step toward creating drugs that impede its virulence, without
interfering with normal cellular function.
Kern summed up: "The fundamental principal of life is that
molecules constantly change over time –that is the definition of
dynamics." |
