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Title: The use of biophysical methods increases success in obtaining liganded crystal structures

Abstract

This paper highlights some of the problems that can arise when attempting to obtain crystal structures of small molecule–protein complexes and how biophysical methods can be used to define and overcome these problems. Many of the techniques mentioned are also applicable to the study of protein–protein complexes and mode-of-action analysis. In attempts to determine the crystal structure of small molecule–protein complexes, a common frustration is the absence of ligand binding once the protein structure has been solved. While the first structure, even with no ligand bound (apo), can be a cause for celebration, the solution of dozens of apo structures can give an unwanted sense of déjà vu. Much time and material is wasted on unsuccessful experiments, which can have a serious impact on productivity and morale. There are many reasons for the lack of observed binding in crystals and this paper highlights some of these. Biophysical methods may be used to confirm and optimize solution conditions to increase the success rate of crystallizing protein–ligand complexes. As there are an overwhelming number of biophysical methods available, some of the factors that need to be considered when choosing the most appropriate technique for a given system are discussed. Finally, a fewmore » illustrative examples where biophysical methods have proven helpful in real systems are given.« less

Authors:
 [1]
  1. Structural and Biophysical Sciences, GlaxoSmithKline Research and Development, Medicines Research Centre, Gunnelswood Road, Stevenage SG1 2NY (United Kingdom)
Publication Date:
OSTI Identifier:
22348004
Resource Type:
Journal Article
Resource Relation:
Journal Name: Acta Crystallographica. Section D: Biological Crystallography; Journal Volume: 63; Journal Issue: Pt 1; Other Information: PMCID: PMC2483471; PUBLISHER-ID: ba5103; PMID: 17164528; OAI: oai:pubmedcentral.nih.gov:2483471; Copyright (c) International Union of Crystallography 2007; This is an open-access article distributed under the terms described at http://journals.iucr.org/services/termsofuse.html.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
Denmark
Language:
English
Subject:
75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; CRYSTAL STRUCTURE; CRYSTALS; LIGANDS; MATHEMATICAL SOLUTIONS; MOLECULES; NUCLEAR MAGNETIC RESONANCE; PROTEIN STRUCTURE; PROTEINS; SOLUTIONS

Citation Formats

Chung, Chun-wa, E-mail: cc16943@gsk.com. The use of biophysical methods increases success in obtaining liganded crystal structures. Denmark: N. p., 2007. Web. doi:10.1107/S0907444906051869.
Chung, Chun-wa, E-mail: cc16943@gsk.com. The use of biophysical methods increases success in obtaining liganded crystal structures. Denmark. doi:10.1107/S0907444906051869.
Chung, Chun-wa, E-mail: cc16943@gsk.com. Mon . "The use of biophysical methods increases success in obtaining liganded crystal structures". Denmark. doi:10.1107/S0907444906051869.
@article{osti_22348004,
title = {The use of biophysical methods increases success in obtaining liganded crystal structures},
author = {Chung, Chun-wa, E-mail: cc16943@gsk.com},
abstractNote = {This paper highlights some of the problems that can arise when attempting to obtain crystal structures of small molecule–protein complexes and how biophysical methods can be used to define and overcome these problems. Many of the techniques mentioned are also applicable to the study of protein–protein complexes and mode-of-action analysis. In attempts to determine the crystal structure of small molecule–protein complexes, a common frustration is the absence of ligand binding once the protein structure has been solved. While the first structure, even with no ligand bound (apo), can be a cause for celebration, the solution of dozens of apo structures can give an unwanted sense of déjà vu. Much time and material is wasted on unsuccessful experiments, which can have a serious impact on productivity and morale. There are many reasons for the lack of observed binding in crystals and this paper highlights some of these. Biophysical methods may be used to confirm and optimize solution conditions to increase the success rate of crystallizing protein–ligand complexes. As there are an overwhelming number of biophysical methods available, some of the factors that need to be considered when choosing the most appropriate technique for a given system are discussed. Finally, a few illustrative examples where biophysical methods have proven helpful in real systems are given.},
doi = {10.1107/S0907444906051869},
journal = {Acta Crystallographica. Section D: Biological Crystallography},
number = Pt 1,
volume = 63,
place = {Denmark},
year = {Mon Jan 01 00:00:00 EST 2007},
month = {Mon Jan 01 00:00:00 EST 2007}
}