Pharmacogenomics of GPCR Drug Targets
Alexander S. Hauser,Alexander S. Hauser,Sreenivas Chavali,Ikuo Masuho,Leonie Johanna Jahn,Kirill A. Martemyanov,David E. Gloriam,M. Madan Babu +7 more
Reads0
Chats0
TLDR
Analysis of UK National Health Service drug prescription and sales data suggests that characterizing GPCR variants could increase prescription precision, improving patients’ quality of life, and relieve the economic and societal burden due to variable drug responsiveness.About:
This article is published in Cell.The article was published on 2018-01-11 and is currently open access. It has received 412 citations till now. The article focuses on the topics: Pharmacogenomics & Population.read more
Citations
More filters
Journal ArticleDOI
Mechanisms of signalling and biased agonism in G protein-coupled receptors
Denise Wootten,Arthur Christopoulos,Maria Marti-Solano,M. Madan Babu,Patrick M. Sexton,Patrick M. Sexton +5 more
TL;DR: Increasing molecular and structural understanding of biased agonism offers the possibility of designing improved GPCR-targeting drugs, and refined classification of drugs according to their pharmacodynamic profiles, which can be linked to receptor structure and predictions of preclinical drug efficacy.
Journal ArticleDOI
GPCRdb in 2018: adding GPCR structure models and ligands.
Gáspár Pándy-Szekeres,Christian Munk,Tsonko M. Tsonkov,Stefan Mordalski,Kasper Harpsøe,Alexander S. Hauser,Andrzej J. Bojarski,David E. Gloriam +7 more
TL;DR: GPCRome-wide homology models of unprecedented quality are reported, and roughly 150 000 GPCR ligands with data on biological activities and commercial availability are provided, to enable scientific investigation for the wider G PCR community.
Journal ArticleDOI
Illuminating G-Protein-Coupling Selectivity of GPCRs.
Asuka Inoue,Asuka Inoue,Francesco Raimondi,Francois Marie Ngako Kadji,Gurdeep Singh,Takayuki Kishi,Akiharu Uwamizu,Yuki Ono,Yuji Shinjo,Satoru Ishida,Nadia Arang,Kouki Kawakami,J. Silvio Gutkind,Junken Aoki,Robert B. Russell +14 more
TL;DR: This work systematically quantified ligand-induced interactions between 148 GPCRs and all 11 unique Gα subunit C termini, and identified sequence-based coupling specificity features, inside and outside the transmembrane domain, which were used to develop a coupling predictor that outperforms previous methods.
Journal ArticleDOI
Common activation mechanism of class A GPCRs.
Qingtong Zhou,Dehua Yang,Meng Wu,Meng Wu,Yu Guo,Yu Guo,Wangjing Guo,Li Zhong,Xiaoqing Cai,Antao Dai,Wonjo Jang,Eugene I. Shakhnovich,Zhi-Jie Liu,Raymond C. Stevens,Nevin A. Lambert,M. Madan Babu,Ming-Wei Wang,Suwen Zhao +17 more
TL;DR: By analyzing the conformational changes in 234 structures from 45 class A GPCRs, this work discovered a common GPCR activation pathway comprising of 34 residue pairs and 35 residues, which unifies previous findings into a common activation mechanism and strings together the scattered key motifs.
Journal ArticleDOI
GPCRdb in 2021: integrating GPCR sequence, structure and function.
Albert J. Kooistra,Stefan Mordalski,Gáspár Pándy-Szekeres,Mauricio Esguerra,Alibek Mamyrbekov,Christian Munk,György M. Keserű,David E. Gloriam +7 more
TL;DR: New and updated GPCRdb resources with a particular focus on integration of sequence, structure and function are described, including a new sequence signature tool for identification of functional residue determinants has been added and two data driven tools to design ligand site mutations and constructs for structure determination have been updated.
References
More filters
Journal ArticleDOI
A global reference for human genetic variation.
Adam Auton,Gonçalo R. Abecasis,David Altshuler,Richard Durbin,David R. Bentley,Aravinda Chakravarti,Andrew G. Clark,Peter Donnelly,Evan E. Eichler,Paul Flicek,Stacey Gabriel,Richard A. Gibbs,Eric D. Green,Matthew E. Hurles,Bartha Maria Knoppers,Jan O. Korbel,Eric S. Lander,Charles Lee,Hans Lehrach,Elaine R. Mardis,Gabor T. Marth,Gil McVean,Deborah A. Nickerson,Jeanette Schmidt,Stephen T. Sherry,Jun Wang,Richard K. Wilson,Eric Boerwinkle,Harsha Doddapaneni,Yi Han,Viktoriya Korchina,Christie Kovar,Sandra L. Lee,Donna M. Muzny,Jeffrey G. Reid,Yiming Zhu,Yuqi Chang,Qiang Feng,Qiang Feng,Xiaodong Fang,Xiaodong Fang,Xiaosen Guo,Xiaosen Guo,Min Jian,Min Jian,Hui Jiang,Hui Jiang,Xin Jin,Tianming Lan,Guoqing Li,Jingxiang Li,Yingrui Li,Shengmao Liu,Xiao Liu,Xiao Liu,Yao Lu,Xuedi Ma,Meifang Tang,Bo Wang,Guangbiao Wang,Honglong Wu,Renhua Wu,Xun Xu,Ye Yin,Dandan Zhang,Wenwei Zhang,Jiao Zhao,Meiru Zhao,Xiaole Zheng,Namrata Gupta,Neda Gharani,Lorraine Toji,Norman P. Gerry,Alissa M. Resch,Jonathan Barker,Laura Clarke,Laurent Gil,Sarah E. Hunt,Gavin Kelman,Eugene Kulesha,Rasko Leinonen,William M. McLaren,Rajesh Radhakrishnan,Asier Roa,Dmitriy Smirnov,Richard Smith,Ian Streeter,Anja Thormann,Iliana Toneva,Brendan Vaughan,Xiangqun Zheng-Bradley,Russell J. Grocock,Sean Humphray,Terena James,Zoya Kingsbury,Ralf Sudbrak,M. Albrecht,Vyacheslav Amstislavskiy,Tatiana A. Borodina,Matthias Lienhard,Florian Mertes,Marc Sultan,Bernd Timmermann,Marie-Laure Yaspo,Lucinda Fulton,Victor Ananiev,Zinaida Belaia,Dimitriy Beloslyudtsev,Nathan Bouk,Chao Chen,Deanna M. Church,Robert M. Cohen,Charles Cook,John Garner,Timothy Hefferon,Mikhail Kimelman,Chunlei Liu,John Lopez,Peter Meric,Chris O’Sullivan,Yuri Ostapchuk,Lon Phan,Sergiy Ponomarov,Valerie A. Schneider,Eugene Shekhtman,Karl Sirotkin,Douglas J. Slotta,Hua Zhang,Senduran Balasubramaniam,John Burton,Petr Danecek,Thomas M. Keane,Anja Kolb-Kokocinski,Shane A. McCarthy,James Stalker,Michael A. Quail,Christopher Davies,Jeremy Gollub,Teresa Webster,Brant Wong,Yiping Zhan,Christopher L. Campbell,Yu Kong,Anthony Marcketta,Fuli Yu,Lilian Antunes,Matthew N. Bainbridge,Aniko Sabo,Zhuoyi Huang,Lachlan J. M. Coin,Lin Fang,Lin Fang,Qibin Li,Zhenyu Li,Haoxiang Lin,Binghang Liu,Ruibang Luo,Haojing Shao,Haojing Shao,Yinlong Xie,Chen Ye,Chang Yu,Fan Zhang,Hancheng Zheng,Zhu Hongmei,Can Alkan,Elif Dal,Fatma Kahveci,Erik Garrison,Deniz Kural,Wan-Ping Lee,Wen Fung Leong,Michael Strömberg,Alistair Ward,Jiantao Wu,Mengyao Zhang,Mark J. Daly,Mark A. DePristo,Robert E. Handsaker,Robert E. Handsaker,Eric Banks,Gaurav Bhatia,Guillermo del Angel,Giulio Genovese,Heng Li,Seva Kashin,Seva Kashin,Steven A. McCarroll,Steven A. McCarroll,James Nemesh,Ryan Poplin,Seungtai Yoon,Jayon Lihm,Vladimir Makarov,Srikanth Gottipati,Alon Keinan,Juan L. Rodriguez-Flores,Tobias Rausch,Markus Hsi-Yang Fritz,Adrian M. Stütz,Kathryn Beal,Avik Datta,Javier Herrero,Graham R. S. Ritchie,Daniel R. Zerbino,Pardis C. Sabeti,Pardis C. Sabeti,Ilya Shlyakhter,Ilya Shlyakhter,Stephen F. Schaffner,Stephen F. Schaffner,Joseph J. Vitti,Joseph J. Vitti,David Neil Cooper,Edward V. Ball,Peter D. Stenson,Bret Barnes,Markus J. Bauer,R. Keira Cheetham,Anthony J. Cox,Michael A. Eberle,Scott Kahn,Lisa Murray,John F. Peden,Richard Shaw,Eimear E. Kenny,Mark A. Batzer,Miriam K. Konkel,Jerilyn A. Walker,Daniel G. MacArthur,Monkol Lek,Ralf Herwig,Li Ding,Daniel C. Koboldt,David E. Larson,Kai Ye,Simon Gravel,Anand Swaroop,Emily Y. Chew,Tuuli Lappalainen,Yaniv Erlich,Melissa Gymrek,Melissa Gymrek,Thomas Willems,Jared T. Simpson,Mark D. Shriver,Jeffrey A. Rosenfeld,Carlos Bustamante,Stephen B. Montgomery,Francisco M. De La Vega,Jake K. Byrnes,Andrew Carroll,Marianne K. DeGorter,Phil Lacroute,Brian K. Maples,Alicia R. Martin,Andrés Moreno-Estrada,Andrés Moreno-Estrada,Suyash Shringarpure,Fouad Zakharia,Eran Halperin,Eran Halperin,Yael Baran,Eliza Cerveira,Jaeho Hwang,Ankit Malhotra,Dariusz Plewczynski,Kamen Radew,Mallory Romanovitch,Chengsheng Zhang,Fiona Hyland,David Craig,Alexis Christoforides,Nils Homer,Tyler Izatt,Ahmet Kurdoglu,Shripad Sinari,Kevin Squire,Chunlin Xiao,Jonathan Sebat,Danny Antaki,Madhusudan Gujral,Amina Noor,Kenny Ye,Esteban G. Burchard,Ryan D. Hernandez,Christopher R. Gignoux,David Haussler,David Haussler,Sol Katzman,W. James Kent,Bryan Howie,Andres Ruiz-Linares,Emmanouil T. Dermitzakis,Emmanouil T. Dermitzakis,Scott E. Devine,Hyun Min Kang,Jeffrey M. Kidd,Thomas W. Blackwell,Sean Caron,Wei Chen,S. Emery,Lars G. Fritsche,Christian Fuchsberger,Goo Jun,Goo Jun,Bingshan Li,Robert H. Lyons,Chris Scheller,Carlo Sidore,Carlo Sidore,Carlo Sidore,Shiya Song,Elzbieta Sliwerska,Daniel Taliun,Adrian Tan,Ryan P. Welch,Mary Kate Wing,Xiaowei Zhan,Philip Awadalla,Philip Awadalla,Alan Hodgkinson,Yun Li,Xinghua Shi,Andrew Quitadamo,Gerton Lunter,Jonathan Marchini,Simon Myers,Claire Churchhouse,Olivier Delaneau,Olivier Delaneau,Anjali Gupta-Hinch,Warren W. Kretzschmar,Zamin Iqbal,Iain Mathieson,Androniki Menelaou,Androniki Menelaou,Andy Rimmer,Dionysia Kiara Xifara,Taras K. Oleksyk,Yunxin Fu,Xiaoming Liu,Momiao Xiong,Lynn B. Jorde,David J. Witherspoon,Jinchuan Xing,Brian L. Browning,Sharon R. Browning,Fereydoun Hormozdiari,Peter H. Sudmant,Ekta Khurana,Chris Tyler-Smith,Cornelis A. Albers,Qasim Ayub,Yuan Chen,Vincenza Colonna,Vincenza Colonna,Luke Jostins,Klaudia Walter,Yali Xue,Mark Gerstein,Alexej Abyzov,Suganthi Balasubramanian,Jieming Chen,Declan Clarke,Yao Fu,Arif Harmanci,Mike Jin,Dong-Hoon Lee,Jeremy Liu,Xinmeng Jasmine Mu,Xinmeng Jasmine Mu,Jing Zhang,Yan Zhang,Christopher Hartl,Khalid Shakir,Jeremiah D. Degenhardt,Sascha Meiers,Benjamin Raeder,Francesco Paolo Casale,Oliver Stegle,Eric-Wubbo Lameijer,Ira M. Hall,Vineet Bafna,Jacob J. Michaelson,Eugene J. Gardner,Ryan E. Mills,Gargi Dayama,Ken Chen,Xian Fan,Zechen Chong,Tenghui Chen,Mark Chaisson,John Huddleston,Maika Malig,Bradley J. Nelson,Nicholas F. Parrish,Ben Blackburne,Sarah J. Lindsay,Zemin Ning,Yujun Zhang,Hugo Y. K. Lam,Cristina Sisu,Danny Challis,Uday S. Evani,James T. Lu,Uma Nagaswamy,Jin Yu,Wangshen Li,Lukas Habegger,Haiyuan Yu,Fiona Cunningham,Ian Dunham,Kasper Lage,Kasper Lage,Jakob Berg Jespersen,Jakob Berg Jespersen,Jakob Berg Jespersen,Heiko Horn,Heiko Horn,Donghoon Kim,Rob DeSalle,Apurva Narechania,Melissa A. Wilson Sayres,Fernando L. Mendez,G. David Poznik,Peter A. Underhill,David Mittelman,Ruby Banerjee,Maria Cerezo,Thomas W. Fitzgerald,Sandra Louzada,Andrea Massaia,Fengtang Yang,Divya Kalra,Walker Hale,Xu Dan,Kathleen C. Barnes,Christine Beiswanger,Hongyu Cai,Hongzhi Cao,Hongzhi Cao,Brenna M. Henn,Danielle Jones,Jane Kaye,Alastair Kent,Angeliki Kerasidou,Rasika A. Mathias,Pilar N. Ossorio,Michael Parker,Charles N. Rotimi,Charmaine D.M. Royal,Karla Sandoval,Yeyang Su,Zhongming Tian,Sarah A. Tishkoff,Marc Via,Yuhong Wang,Huanming Yang,Ling Yang,Jiayong Zhu,Walter F. Bodmer,Gabriel Bedoya,Zhiming Cai,Yang Gao,Jiayou Chu,Leena Peltonen,Andrés C. García-Montero,Alberto Orfao,Julie Dutil,Juan Carlos Martínez-Cruzado,R. Mathias,Anselm Hennis,Harold Watson,Colin A. McKenzie,Firdausi Qadri,Regina C. LaRocque,Xiaoyan Deng,Danny Asogun,Onikepe A. Folarin,Christian T. Happi,Omonwunmi Omoniwa,Matt Stremlau,Matt Stremlau,Ridhi Tariyal,Ridhi Tariyal,M Jallow,M Jallow,Fatoumatta Sisay Joof,Fatoumatta Sisay Joof,Tumani Corrah,Tumani Corrah,Kirk A. Rockett,Kirk A. Rockett,Dominic P. Kwiatkowski,Dominic P. Kwiatkowski,Jaspal S. Kooner,Tran Tinh Hien,Sarah J. Dunstan,Sarah J. Dunstan,Nguyen ThuyHang,Richard Fonnie,Robert F. Garry,Lansana Kanneh,Lina M. Moses,John S. Schieffelin,Donald S. Grant,Carla Gallo,Giovanni Poletti,Danish Saleheen,Asif Rasheed,Lisa D. Brooks,Adam Felsenfeld,Jean E. McEwen,Yekaterina Vaydylevich,Audrey Duncanson,Michael Dunn,Jeffery A. Schloss +517 more
TL;DR: The 1000 Genomes Project set out to provide a comprehensive description of common human genetic variation by applying whole-genome sequencing to a diverse set of individuals from multiple populations, and has reconstructed the genomes of 2,504 individuals from 26 populations using a combination of low-coverage whole-generation sequencing, deep exome sequencing, and dense microarray genotyping.
Journal ArticleDOI
Analysis of protein-coding genetic variation in 60,706 humans
Monkol Lek,Konrad J. Karczewski,Konrad J. Karczewski,Eric Vallabh Minikel,Eric Vallabh Minikel,Kaitlin E. Samocha,Eric Banks,Timothy Fennell,Anne H. O’Donnell-Luria,Anne H. O’Donnell-Luria,Anne H. O’Donnell-Luria,James S. Ware,Andrew J. Hill,Andrew J. Hill,Andrew J. Hill,Beryl B. Cummings,Beryl B. Cummings,Taru Tukiainen,Taru Tukiainen,Daniel P. Birnbaum,Jack A. Kosmicki,Laramie E. Duncan,Laramie E. Duncan,Karol Estrada,Karol Estrada,Fengmei Zhao,Fengmei Zhao,James Zou,Emma Pierce-Hoffman,Emma Pierce-Hoffman,Joanne Berghout,David Neil Cooper,Nicole A. Deflaux,Mark A. DePristo,Ron Do,Jason Flannick,Jason Flannick,Menachem Fromer,Laura D. Gauthier,Jackie Goldstein,Jackie Goldstein,Namrata Gupta,Daniel P. Howrigan,Daniel P. Howrigan,Adam Kiezun,Mitja I. Kurki,Mitja I. Kurki,Ami Levy Moonshine,Pradeep Natarajan,Lorena Orozco,Gina M. Peloso,Gina M. Peloso,Ryan Poplin,Manuel A. Rivas,Valentin Ruano-Rubio,Samuel A. Rose,Douglas M. Ruderfer,Khalid Shakir,Peter D. Stenson,Christine Stevens,Brett Thomas,Brett Thomas,Grace Tiao,María Teresa Tusié-Luna,Ben Weisburd,Hong-Hee Won,Dongmei Yu,David Altshuler,David Altshuler,Diego Ardissino,Michael Boehnke,John Danesh,Stacey Donnelly,Roberto Elosua,Jose C. Florez,Jose C. Florez,Stacey Gabriel,Gad Getz,Gad Getz,Stephen J. Glatt,Christina M. Hultman,Sekar Kathiresan,Markku Laakso,Steven A. McCarroll,Steven A. McCarroll,Mark I. McCarthy,Mark I. McCarthy,Dermot P.B. McGovern,Ruth McPherson,Benjamin M. Neale,Benjamin M. Neale,Aarno Palotie,Shaun Purcell,Danish Saleheen,Jeremiah M. Scharf,Pamela Sklar,Patrick F. Sullivan,Patrick F. Sullivan,Jaakko Tuomilehto,Ming T. Tsuang,Hugh Watkins,Hugh Watkins,James G. Wilson,Mark J. Daly,Mark J. Daly,Daniel G. MacArthur,Daniel G. MacArthur +106 more
TL;DR: The aggregation and analysis of high-quality exome (protein-coding region) DNA sequence data for 60,706 individuals of diverse ancestries generated as part of the Exome Aggregation Consortium (ExAC) provides direct evidence for the presence of widespread mutational recurrence.
Journal ArticleDOI
SIFT: predicting amino acid changes that affect protein function
Pauline C. Ng,Steven Henikoff +1 more
TL;DR: SIFT is a program that predicts whether an amino acid substitution affects protein function so that users can prioritize substitutions for further study and can distinguish between functionally neutral and deleterious amino acid changes in mutagenesis studies and on human polymorphisms.
Journal ArticleDOI
Predicting Functional Effect of Human Missense Mutations Using PolyPhen-2
TL;DR: PolyPhen‐2 (Polymorphism Phenotyping v2), available as software and via a Web server, predicts the possible impact of amino acid substitutions on the stability and function of human proteins using structural and comparative evolutionary considerations.
Journal ArticleDOI
Crystal structure of the β2 adrenergic receptor-Gs protein complex.
Søren G. F. Rasmussen,Brian T. DeVree,Yaozhong Zou,Andrew C. Kruse,Ka Young Chung,Tong Sun Kobilka,Foon Sun Thian,Pil Seok Chae,Els Pardon,Els Pardon,Diane M. Calinski,Jesper Mosolff Mathiesen,Syed T. A. Shah,Joseph A. Lyons,Martin Caffrey,Samuel H. Gellman,Jan Steyaert,Jan Steyaert,Georgios Skiniotis,William I. Weis,Roger K. Sunahara,Brian K. Kobilka +21 more
TL;DR: This crystal structure represents the first high-resolution view of transmembrane signalling by a GPCR and the most surprising observation is a major displacement of the α-helical domain of Gαs relative to the Ras-like GTPase domain.
Related Papers (5)
Crystal structure of the β2 adrenergic receptor-Gs protein complex.
Søren G. F. Rasmussen,Brian T. DeVree,Yaozhong Zou,Andrew C. Kruse,Ka Young Chung,Tong Sun Kobilka,Foon Sun Thian,Pil Seok Chae,Els Pardon,Els Pardon,Diane M. Calinski,Jesper Mosolff Mathiesen,Syed T. A. Shah,Joseph A. Lyons,Martin Caffrey,Samuel H. Gellman,Jan Steyaert,Jan Steyaert,Georgios Skiniotis,William I. Weis,Roger K. Sunahara,Brian K. Kobilka +21 more