Identifying ligand-binding hot spots in proteins using brominated fragments

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

High-quality crystals of Thermus thermophilus EF-Tu in the GTP-bound conformation at 1.7-2.7 Å resolution were used to test 18 small organic molecules, all brominated for confident identification in the anomalous difference maps. From this relatively small collection, it was possible to identify a small molecule bound in the functionally important tRNA CCA-end binding pocket. The antibiotic GE2270 A is known to interact with the same pocket in EF-Tu and to disrupt the association with tRNA. Bromide could be located from peaks in the anomalous map in data truncated to very low resolution without refining the structure. Considering the speed with which diffraction data can be collected today, it is proposed that it is worthwhile to collect the extra data from fragment screens while crystals are at hand to increase the knowledge of biological function and drug binding in an experimental structural context.
Original languageEnglish
JournalActa Crystallographica. Section F: Structural Biology and Crystallization Communications Online
Volume69
IssuePt 9
Pages (from-to)1060-1065
Number of pages6
ISSN2053-230X
DOIs
Publication statusPublished - Sep 2013

See relations at Aarhus University Citationformats

ID: 56336100