Identifying ligand-binding hot spots in proteins using brominated fragments

Morten K Grøftehauge; Martin O Therkelsen; Rolf Taaning; Troels Skrydstrup; J Preben Morth; Poul Nissen

doi:10.1107/S1744309113018551

Identifying ligand-binding hot spots in proteins using brominated fragments

Morten K Grøftehauge, Martin O Therkelsen, Rolf Taaning, Troels Skrydstrup, J Preben Morth, Poul Nissen

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

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Abstract

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 language	English
Journal	Acta Crystallographica. Section F: Structural Biology and Crystallization Communications Online
Volume	69
Issue	Pt 9
Pages (from-to)	1060-1065
Number of pages	6
ISSN	2053-230X
DOIs	https://doi.org/10.1107/S1744309113018551
Publication status	Published - Sept 2013

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title = "Identifying ligand-binding hot spots in proteins using brominated fragments",

abstract = "High-quality crystals of Thermus thermophilus EF-Tu in the GTP-bound conformation at 1.7-2.7 {\AA} 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.",

author = "Gr{\o}ftehauge, \{Morten K\} and Therkelsen, \{Martin O\} and Rolf Taaning and Troels Skrydstrup and Morth, \{J Preben\} and Poul Nissen",

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journal = "Acta Crystallographica. Section F: Structural Biology and Crystallization Communications Online",

issn = "2053-230X",

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Identifying ligand-binding hot spots in proteins using brominated fragments. / Grøftehauge, Morten K; Therkelsen, Martin O; Taaning, Rolf et al.
In: Acta Crystallographica. Section F: Structural Biology and Crystallization Communications Online, Vol. 69, No. Pt 9, 09.2013, p. 1060-1065.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Identifying ligand-binding hot spots in proteins using brominated fragments

AU - Grøftehauge, Morten K

AU - Therkelsen, Martin O

AU - Taaning, Rolf

AU - Skrydstrup, Troels

AU - Morth, J Preben

AU - Nissen, Poul

PY - 2013/9

Y1 - 2013/9

N2 - 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.

AB - 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.

U2 - 10.1107/S1744309113018551

DO - 10.1107/S1744309113018551

M3 - Journal article

C2 - 23989163

SN - 2053-230X

VL - 69

SP - 1060

EP - 1065

JO - Acta Crystallographica. Section F: Structural Biology and Crystallization Communications Online

JF - Acta Crystallographica. Section F: Structural Biology and Crystallization Communications Online

IS - Pt 9

ER -

Identifying ligand-binding hot spots in proteins using brominated fragments

Abstract

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