Structural genomics for membrane proteins

Abstract

Structure-based drug discovery has proven useful in improving and shortening the drug development process. The approach of structural genomics to study a large number of targets in parallel has been commonly applied to protein families and even whole genomes. Paradoxically, although membrane proteins represent the largest type of drug targets, up to 70% today, determination of their structure has been modest compared to that of soluble proteins. Because membrane proteins are important for drug discovery an emphasis has been placed on developing technologies and methods to determine membrane protein structures. Several structural genomics initiatives have been established, focusing on the structural biology of membrane proteins.

Biology and application of alphaviruses in gene therapy

“…Recently, the SFV system has been applied in a structural genomics program to overexpress 100 GPCRs with the aim of solubilization, purification and ultimately crystallization of GPCRs. 10 …”

“…The first step towards gene therapy application was the demonstration of high transduction rates of various Large-scale production Drug screening, structural biology 9,10 Primary neurons Localization, electrophysiology 11 Hippocampal slices Localization, electrophysiology 12,13 In vivo, rat brain Localization, duration 16 Gene therapy Cancer vaccines Tumor protection, tumor regression 20 Tumor cell lines Transduction, cell killing 17,18 Intratumoral injection Tumor regression 23,24 Liposome-encapsulation Tumor-targeted gene delivery, therapy 28 18 Clearly, the infection rate was modest, although a bystander effect was observed for the therapeutic TK (thymidine kinase) after ganciclovir treatment. Another application of alphaviruses for cancer therapy has been vaccination with tumor antigens.…”

Genomics and proteomics: of hares, tortoises and the complexity of tortoises

“…As of early 2012, the Protein Data Bank of Transmembrane Proteins held over 83,700 structures of which 1690 transmembrane proteins have been predicted so far [32,33]. Membrane proteins are of particular importance, since over 60% of current drugs are based on targeting this group of proteins [34].…”

▪ Introduction

“…Such membrane proteins are a large component of the genome and include many proteins of great physiological importance, such as ion channels and receptors (Lundstrom 2006). Over recent years many more membrane proteins have been crystallized (Figure 1.3B) and their structures elucidated by X-rays, some of the most important ones being PS-I (Fromme and Mathis 2004)and bacteriorhodopsin (Grigorieff, Ceska et al 1996).…”