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Bright lights: Mystery of glowing antibody solved by Scripps research scientists
Date:2/28/2008

n observed for stilbene and was totally unexpected, especially since stilbene is basically the E. coli of photochemistry, as it is extremely well characterized and understood.

The fact that the EP2-19G2-stilbene complex emits a bright luminescence was first described in a Scripps Research study published in the October 13, 2000 edition (Volume 290, Number 5490) of the journal Science. The underlying mechanism had remained unknown until now.

A Perfect Match, A Perfect Storm

When EP2-19G2 binds stilbene, the antibody itself coordinates the joining or stacking of stilbene with a deeply buried tryptophan residue at the active site. In other fluorescent antibodies, such a stacking interaction does not exist. After exposure to UV, electron transfer between stilbene and tryptophan occurs deep within the 19G2 protein matrix.

Kim Janda, who is Ely R. Callaway, Jr. Chair in Chemistry, member of The Skaggs Institute for Chemical Biology, and director of the Worm Institute for Research and Medicine at Scripps Research, led the initial research into EP2-19G2 and was part of the new study. He described the importance of the combination this way: This may be a perfect molecular storm. When the tryptophan residue and stilbene are matched in EP2-19G2, this perfect alignment creates a different luminescence pathway than is seen in other related antibodies.

Unlike in other complexes, this antibody reacts with stilbene in the excited state. Antibody EP2-19G2 is deeply penetrated by the stilbene molecule and the special constellation of the stilbene-tryptophan pairing sets this antibody apart from other antibody-stilbene complexes, where binding merely enhances stilbene fluorescence by inhibiting photoisomerization, the dominant nonradiative decay pathway of stilbene in solution.

In fact, the unusual binding mode of stilbene in EP2-19GE2 is enabled by a non-canonical interface of the variable heavy and light chains of the anti
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Contact: Mika Benedyk
mbenedyk@scripps.edu
858-784-2052
Scripps Research Institute
Source:Eurekalert

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