Tryptophan-based fluorophores for studying protein conformational changes.

Abstract:

:With the continuing interest in deciphering the interplay between protein function and conformational changes, small fluorescence probes will be especially useful for tracking changes in the crowded protein interior space. Presently, we describe the potential utility of six unnatural amino acid fluorescence donors structurally related to tryptophan and show how they can be efficiently incorporated into a protein as fluorescence probes. We also examine the various photophysical properties of the new Trp analogues, which are significantly redshifted in their fluorescence spectra relative to tryptophan. In general, the Trp analogues were well tolerated when inserted into Escherichia coli DHFR, and did not perturb enzyme activity, although substitution for Trp22 did result in a diminution in DHFR activity. Further, it was demonstrated that D and E at position 37 formed efficient FRET pairs with acridon-2-ylalanine (Acd) at position 17. The same was also true for a DHFR construct containing E at position 79 and Acd at position 17. Together, these findings demonstrate that these tryptophan analogues can be introduced into DHFR with minimal disruption of function, and that they can be employed for the selective study of targeted conformational changes in proteins, even in the presence of unmodified tryptophans.

journal_name

Bioorg Med Chem

authors

Talukder P,Chen S,Liu CT,Baldwin EA,Benkovic SJ,Hecht SM

doi

10.1016/j.bmc.2014.09.015

subject

Has Abstract

pub_date

2014-11-01 00:00:00

pages

5924-34

issue

21

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(14)00651-8

journal_volume

22

pub_type

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