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 Chemjournal_title
Bioorganic & medicinal chemistryauthors
Talukder P,Chen S,Liu CT,Baldwin EA,Benkovic SJ,Hecht SMdoi
10.1016/j.bmc.2014.09.015subject
Has Abstractpub_date
2014-11-01 00:00:00pages
5924-34issue
21eissn
0968-0896issn
1464-3391pii
S0968-0896(14)00651-8journal_volume
22pub_type
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