More Chemical Evidence for an Antibody Killing Mechanism
By Jason Socrates
Bardi
Last year Professor Richard A. Lerner, Associate Professor
Paul Wentworth, Jr., and a team of investigators at The Scripps
Research Institute (TSRI) reported that antibodies can themselves
destroy bacteria, and that when they do they appear to produce
the reactive gas ozone.
The ozone, which was never considered part of biology before,
seems to be part of a previously unrecognized killing mechanism
that would enhance the defensive role of antibodies by allowing
them to subject pathogens to oxidation and participate directly
in their killing. Previously, antibodies were believed only
to signal an immune response.
Now the same team is reporting, in an article published
online by the Proceedings of the National Academy of Sciences,
that antibodies can chemically modify their bound antigens
during the antibody-catalyzed water oxidation pathway. More
specifically, they regioselectively hydroxylate benzoic acid—when
it is bound within the antibody binding site. Furthermore,
they found a hydroxylated tryptophan residue in the interfacial
domain of one of the antibodies they looked at, which offered
further evidence that this region of the antibody structure
is where the process is taking place.
By showing that antibodies can chemically modify something
to which they are bound and that this modification may be
taking place where the antibody binds to antigen, they are
providing further evidence for their mechanistic interpretation
of how antibodies kill bacteria.
The latest study suggests that the antibodies may be producing
a long-lived hydroxy radical (HO•) surrogate, the hydrotrioxy
radical (HO3•), that diffuses along a channel
from the interfacial region, between the constant and variable
domains, to the combining site of the antibody molecule. When
the hydroxyl radical goes through the channel, it can either
react with the bacterial antigen or trigger a radical cascade
on the surface of the bacterial membrane.
To read the article, "Evidence for the production of trioxygen
species during antibody-catalyzed chemical modification of
antigens" by Paul Wentworth, Jr., Anita D. Wentworth, Xueyong
Zhu, Ian A. Wilson, Kim D. Janda, Albert Eschenmoser, and
Richard A. Lerner, please see:
http://www.pnas.org/cgi/content/abstract/0437831100v1.
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