Can Predicted Protein 3D Structures Provide Reliable Insights into whether Missense Variants Are Disease Associated
Sirawit Ittisoponpisan,Suhail A. Islam,Tarun Khanna,Eman Alhuzimi,Alessia David,Michael J.E. Sternberg +5 more
TLDR
This work assesses whether a missense variant is structurally damaging by using experimental and predicted structures and shows that 40% of the 1965 disease-associated missense variants analyzed have aStructurally damaging change in the mutant structure.About:
This article is published in Journal of Molecular Biology.The article was published on 2019-05-17 and is currently open access. It has received 284 citations till now. The article focuses on the topics: Protein structure prediction.read more
Citations
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Experimental evidence for enhanced receptor binding by rapidly spreading SARS-CoV-2 variants.
TL;DR: In this article, the authors experimentally established that RBD containing the N501Y mutation results in 7-fold stronger binding to the angiotensin converting enzyme 2 (ACE2) receptor than wild type RBD.
Journal ArticleDOI
Functional interrogation of DNA damage response variants with base editing screens
Raquel Cuella-Martin,Samuel B. Hayward,Xiao Fan,Xiao Chen,Jen-Wei Huang,Angelo Taglialatela,Giuseppe Leuzzi,Junfei Zhao,Raul Rabadan,Chao Lu,Yufeng Shen,Alberto Ciccia +11 more
TL;DR: In this article, using CRISPR-dependent cytosine base editing screens, the authors identify > 2,000 sgRNAs that generate nucleotide variants in 86 DDR genes, resulting in altered cellular fitness upon DNA damage.
Journal ArticleDOI
PDBe-KB: a community-driven resource for structural and functional annotations
Mihaly Varadi,John M. Berrisford,Mandar Deshpande,Sreenath Nair,Aleksandras Gutmanas,David R. Armstrong,Lukáš Pravda,Bissan Al-Lazikani,Stephen Anyango,Geoffrey J. Barton,Karel Berka,Tom L. Blundell,Neera Borkakoti,Jose M. Dana,Sayoni Das,Sucharita Dey,Patrizio Di Micco,Franca Fraternali,Toby J. Gibson,Manuela Helmer-Citterich,David Hoksza,David Hoksza,Liang-Chin Huang,Rishabh Jain,Harry Jubb,Christos C. Kannas,Natarajan Kannan,Jaroslav Koča,Radoslav Krivak,Manjeet Kumar,Emmanuel D. Levy,Fábio Madeira,Mallur S. Madhusudhan,Henry J Martell,Stuart A. MacGowan,Jake E McGreig,Saqib Mir,Abhik Mukhopadhyay,Luca Parca,Typhaine Paysan-Lafosse,Leandro G Radusky,António J. M. Ribeiro,Luis Serrano,Ian Sillitoe,Gulzar Singh,Petr Škoda,Radka Svobodová,Jonathan D. Tyzack,Alfonso Valencia,Eloy Villasclaras Fernandez,Wim F. Vranken,Mark N. Wass,Janet M. Thornton,Michael J.E. Sternberg,Christine A. Orengo,Sameer Velankar +55 more
TL;DR: The guidelines of this collaborative effort, the current status of contributed data, and the PDBe-KB infrastructure, which includes the data exchange format, the deposition system for added value annotations, the distributable database containing the assembledData, and programmatic access endpoints are described.
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VarSite: Disease variants and protein structure
Roman A. Laskowski,James Stephenson,James Stephenson,Ian Sillitoe,Christine A. Orengo,Janet M. Thornton +5 more
TL;DR: VarSite is a web server mapping known disease‐associated variants from UniProt and ClinVar, together with natural variants from gnomAD, onto protein 3D structures in the Protein Data Bank, and provides both an overview for each human protein, as well as a report for any specific variant of interest.
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In Silico Investigation of the New UK (B.1.1.7) and South African (501Y.V2) SARS-CoV-2 Variants with a Focus at the ACE2-Spike RBD Interface.
TL;DR: It is found that the N501Y replacement in this region of the interface (present in both the UK and South African strains) should be favorable for the interaction with ACE2, while the K417N and E484K substitutions (South African strain) would seem neutral or even unfavorable.
References
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