Abstract
G protein-coupled receptors (GPCRs), a family of seven-transmembrane receptors, are among the most important drug targets with over half of all marketed drugs targeting the family. However, only a handful of easily druggable GPCRs are successfully targeted by pharmaceuticals. Efforts to shift this intensive focus to other, more recalcitrant GPCR targets will increasingly draw on new information such as structural details, which have until recently proven tremendously challenging to gather for this class of protein receptors due to the difficulties in obtaining diffraction-quality crystals. Recently, the development and application of lipidic cubic phase (LCP) technology has reduced one major hurdle for crystallization of GPCRs, with 22 unique receptors being structurally characterized from LCP grown crystals over the span of seven years. This review focuses on the technological improvements for LCP that have led to its successful utilization on the GPCR family, including the most recent combination of LCP with the X-ray free-electron laser that dramatically reduces requirements on crystal size, and holds significant promise for shortening timelines for structure determination and for accessing previously unattainable structures such as those of signaling complexes.
Keywords: G protein-coupled receptor (GPCR), lipidic cubic phase (LCP), membrane proteins, Serial Femtosecond Crystallography (SFX), structure-based drug design, X-ray free-electron laser (XFEL).
Current Pharmaceutical Biotechnology
Title:GPCR Crystallization Using Lipidic Cubic Phase Technique
Volume: 15 Issue: 10
Author(s): Xin Yin, Henghao Xu, Michael Hanson and Wei Liu
Affiliation:
Keywords: G protein-coupled receptor (GPCR), lipidic cubic phase (LCP), membrane proteins, Serial Femtosecond Crystallography (SFX), structure-based drug design, X-ray free-electron laser (XFEL).
Abstract: G protein-coupled receptors (GPCRs), a family of seven-transmembrane receptors, are among the most important drug targets with over half of all marketed drugs targeting the family. However, only a handful of easily druggable GPCRs are successfully targeted by pharmaceuticals. Efforts to shift this intensive focus to other, more recalcitrant GPCR targets will increasingly draw on new information such as structural details, which have until recently proven tremendously challenging to gather for this class of protein receptors due to the difficulties in obtaining diffraction-quality crystals. Recently, the development and application of lipidic cubic phase (LCP) technology has reduced one major hurdle for crystallization of GPCRs, with 22 unique receptors being structurally characterized from LCP grown crystals over the span of seven years. This review focuses on the technological improvements for LCP that have led to its successful utilization on the GPCR family, including the most recent combination of LCP with the X-ray free-electron laser that dramatically reduces requirements on crystal size, and holds significant promise for shortening timelines for structure determination and for accessing previously unattainable structures such as those of signaling complexes.
Export Options
About this article
Cite this article as:
Yin Xin, Xu Henghao, Hanson Michael and Liu Wei, GPCR Crystallization Using Lipidic Cubic Phase Technique, Current Pharmaceutical Biotechnology 2014; 15 (10) . https://dx.doi.org/10.2174/1389201015666140922110325
DOI https://dx.doi.org/10.2174/1389201015666140922110325 |
Print ISSN 1389-2010 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4316 |
Call for Papers in Thematic Issues
Artificial Intelligence in Bioinformatics
Bioinformatics is an interdisciplinary field that analyzes and explores biological data. This field combines biology and information system. Artificial Intelligence (AI) has attracted great attention as it tries to replicate human intelligence. It has become common technology for analyzing and solving complex data and problems and encompasses sub-fields of machine ...read more
Latest Advancements in Biotherapeutics
The scope of this thematic issue is to comprehensively explore the rapidly evolving landscape of biotherapeutics, emphasizing breakthroughs in precision medicine. Encompassing diverse therapeutic modalities, the issue will delve into the latest developments in monoclonal antibodies, CRISPR/Cas gene editing, CAR-T cell therapies, and innovative drug delivery systems, such as nanoparticle-based ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
In Search of Novel and Therapeutically Significant Melatoninergic Ligands
Recent Patents on CNS Drug Discovery (Discontinued) Role of Retinoids, Rexinoids and Thyroid Hormone in the Expression of Cytochrome P450 Enzymes
Current Drug Metabolism Anti-Platelet Treatment of Middle-Sized Abdominal Aortic Aneurysms
Current Vascular Pharmacology Nanoceria: A Novel Cytoprotective Drug Delivery Carrier
Current Nanomedicine Connexins in Renal Endothelial Function and Dysfunction
Cardiovascular & Hematological Disorders-Drug Targets Tanshinone IIA: Pharmacology, Total Synthesis, and Progress in Structure-modifications
Current Medicinal Chemistry Identification of Genes for a Complex Trait: Examples from Hypertension
Current Pharmaceutical Biotechnology Tumor Immune Escape Mechanisms that Operate During Metastasis
Current Pharmaceutical Biotechnology Glucocorticoid Regulates Parkin Expression in Mouse Frontal Cortex: Implications in Schizophrenia
Current Neuropharmacology Structure-Based Virtual Ligand Screening: Recent Success Stories
Combinatorial Chemistry & High Throughput Screening Therapeutic Use of MicroRNAs in Cancer
Anti-Cancer Agents in Medicinal Chemistry Development of Proteinase-Activated Receptor 1 Antagonists as Therapeutic Agents for Thrombosis, Restenosis and Inflammatory Diseases
Current Pharmaceutical Design Novel Artemisinin-Derived Dimers: Synthesis and Evaluation of Anti-cancer Activities
Letters in Drug Design & Discovery Hereditary Haemorrhagic Teleangiectasia: Diagnostic Imaging of Visceral Involvement
Current Pharmaceutical Design Alginates in Pharmaceutics and Biomedicine: Is the Future so Bright?
Current Pharmaceutical Design Atypical GTPases as Drug Targets
Anti-Cancer Agents in Medicinal Chemistry Trimethylamine: Metabolic, Pharmacokinetic and Safety Aspects
Current Drug Metabolism Vascular Effects of Estrogenic Menopausal Hormone Therapy
Reviews on Recent Clinical Trials Arterial Dilatation-Related Diseases: The Prerequisite Condition of Arterial Elastic Tissue Damage and Endovascular Treatment
Recent Patents on Medical Imaging Studies with Emulsion Containing trans-resveratrol: in vitro Release Profile and ex vivo Human Skin Permeation
Current Drug Delivery