Recent Advances in Structure, Function, and Pharmacology of Class A Lipid GPCRs: Opportunities and Challenges for Drug Discovery
Great progress has been made over the past decade in understanding the structural, functional, and pharmacological diversity of lipid GPCRs. From the first determination of the crystal structure of bovine rhodopsin in 2000, much progress has been made in the field of GPCR structural biology. The ext...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-12-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/1/12 |
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| author | R. N. V. Krishna Deepak Ravi Kumar Verma Yossa Dwi Hartono Wen Shan Yew Hao Fan |
| author_facet | R. N. V. Krishna Deepak Ravi Kumar Verma Yossa Dwi Hartono Wen Shan Yew Hao Fan |
| author_sort | R. N. V. Krishna Deepak |
| collection | DOAJ |
| description | Great progress has been made over the past decade in understanding the structural, functional, and pharmacological diversity of lipid GPCRs. From the first determination of the crystal structure of bovine rhodopsin in 2000, much progress has been made in the field of GPCR structural biology. The extraordinary progress in structural biology and pharmacology of GPCRs, coupled with rapid advances in computational approaches to study receptor dynamics and receptor-ligand interactions, has broadened our comprehension of the structural and functional facets of the receptor family members and has helped usher in a modern age of structure-based drug design and development. First, we provide a primer on lipid mediators and lipid GPCRs and their role in physiology and diseases as well as their value as drug targets. Second, we summarize the current advancements in the understanding of structural features of lipid GPCRs, such as the structural variation of their extracellular domains, diversity of their orthosteric and allosteric ligand binding sites, and molecular mechanisms of ligand binding. Third, we close by collating the emerging paradigms and opportunities in targeting lipid GPCRs, including a brief discussion on current strategies, challenges, and the future outlook. |
| first_indexed | 2024-03-10T00:44:56Z |
| format | Article |
| id | doaj.art-38d6388569594c49802b2c5b5a978725 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T00:44:56Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-38d6388569594c49802b2c5b5a9787252023-11-23T15:00:42ZengMDPI AGPharmaceuticals1424-82472021-12-011511210.3390/ph15010012Recent Advances in Structure, Function, and Pharmacology of Class A Lipid GPCRs: Opportunities and Challenges for Drug DiscoveryR. N. V. Krishna Deepak0Ravi Kumar Verma1Yossa Dwi Hartono2Wen Shan Yew3Hao Fan4Bioinformatics Institute, A*STAR, 30 Biopolis Street, Matrix #07-01, Singapore 138671, SingaporeBioinformatics Institute, A*STAR, 30 Biopolis Street, Matrix #07-01, Singapore 138671, SingaporeBioinformatics Institute, A*STAR, 30 Biopolis Street, Matrix #07-01, Singapore 138671, SingaporeSynthetic Biology Translational Research Programme, Yong Loo Lin School of Medicine, National University of Singapore, 14 Medical Drive, Singapore 117599, SingaporeBioinformatics Institute, A*STAR, 30 Biopolis Street, Matrix #07-01, Singapore 138671, SingaporeGreat progress has been made over the past decade in understanding the structural, functional, and pharmacological diversity of lipid GPCRs. From the first determination of the crystal structure of bovine rhodopsin in 2000, much progress has been made in the field of GPCR structural biology. The extraordinary progress in structural biology and pharmacology of GPCRs, coupled with rapid advances in computational approaches to study receptor dynamics and receptor-ligand interactions, has broadened our comprehension of the structural and functional facets of the receptor family members and has helped usher in a modern age of structure-based drug design and development. First, we provide a primer on lipid mediators and lipid GPCRs and their role in physiology and diseases as well as their value as drug targets. Second, we summarize the current advancements in the understanding of structural features of lipid GPCRs, such as the structural variation of their extracellular domains, diversity of their orthosteric and allosteric ligand binding sites, and molecular mechanisms of ligand binding. Third, we close by collating the emerging paradigms and opportunities in targeting lipid GPCRs, including a brief discussion on current strategies, challenges, and the future outlook.https://www.mdpi.com/1424-8247/15/1/12lipid GPCRligand accessorthosteric and allosteric binding sitesdrug discoveryantibodycomputational methods |
| spellingShingle | R. N. V. Krishna Deepak Ravi Kumar Verma Yossa Dwi Hartono Wen Shan Yew Hao Fan Recent Advances in Structure, Function, and Pharmacology of Class A Lipid GPCRs: Opportunities and Challenges for Drug Discovery Pharmaceuticals lipid GPCR ligand access orthosteric and allosteric binding sites drug discovery antibody computational methods |
| title | Recent Advances in Structure, Function, and Pharmacology of Class A Lipid GPCRs: Opportunities and Challenges for Drug Discovery |
| title_full | Recent Advances in Structure, Function, and Pharmacology of Class A Lipid GPCRs: Opportunities and Challenges for Drug Discovery |
| title_fullStr | Recent Advances in Structure, Function, and Pharmacology of Class A Lipid GPCRs: Opportunities and Challenges for Drug Discovery |
| title_full_unstemmed | Recent Advances in Structure, Function, and Pharmacology of Class A Lipid GPCRs: Opportunities and Challenges for Drug Discovery |
| title_short | Recent Advances in Structure, Function, and Pharmacology of Class A Lipid GPCRs: Opportunities and Challenges for Drug Discovery |
| title_sort | recent advances in structure function and pharmacology of class a lipid gpcrs opportunities and challenges for drug discovery |
| topic | lipid GPCR ligand access orthosteric and allosteric binding sites drug discovery antibody computational methods |
| url | https://www.mdpi.com/1424-8247/15/1/12 |
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