4.8 Article

Drug Design for G-Protein-Coupled Receptors by a Ligand-Based NMR Method

Journal

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 49, Issue 8, Pages 1426-1429

Publisher

WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.200905102

Keywords

drug design; G-protein-coupled receptors; NMR spectroscopy; structure-activity relationships

Ask authors/readers for more resources

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.8
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

Article Multidisciplinary Sciences

Molecular mechanism of SHP2 activation by PD-1 stimulation

M. Marasco, A. Berteotti, J. Weyershaeuser, N. Thorausch, J. Sikorska, J. Krausze, H. J. Brandt, J. Kirkpatrick, P. Rios, W. W. Schamel, M. Koehn, T. Carlomagno

SCIENCE ADVANCES (2020)

Article Biophysics

1H, 13C, 15N chemical shift assignments of SHP2 SH2 domains in complex with PD-1 immune-tyrosine motifs

Michelangelo Marasco, John P. Kirkpatrick, Teresa Carlomagno

BIOMOLECULAR NMR ASSIGNMENTS (2020)

Article Biochemistry & Molecular Biology

High-resolution structure of eukaryotic Fibrillarin interacting with Nop56 amino-terminal domain

Simone Hoefler, Peer Lukat, Wulf Blankenfeldt, Teresa Carlomagno

Summary: 2'-O-methylation in rRNA plays a role in stability and folding, with the Box C/D RNP enzyme accomplishing this modification in an RNA-guided manner. Differences in protein interaction modes between Nop56 and Nop1 exist in eukaryotes and archaea.
Article Biophysics

1H, 13C, and 15N backbone chemical-shift assignments of SARS-CoV-2 non-structural protein 1 (leader protein)

Ying Wang, John Kirkpatrick, Susanne zur Lage, Sophie M. Korn, Konstantin Neissner, Harald Schwalbe, Andreas Schlundt, Teresa Carlomagno

Summary: The ongoing COVID-19 pandemic has posed a global health crisis, requiring urgent scientific research to identify new drug targets for treatment. The report provides near-complete backbone chemical-shift assignments of full-length SARS-CoV-2 Nsp1, offering insights into the structure and dynamics of Nsp1 for further NMR-based investigations.

BIOMOLECULAR NMR ASSIGNMENTS (2021)

Article Biochemistry & Molecular Biology

Large-Scale Recombinant Production of the SARS-CoV-2 Proteome for High-Throughput and Structural Biology Applications

Nadide Altincekic, Sophie Marianne Korn, Nusrat Shahin Qureshi, Marie Dujardin, Marti Ninot-Pedrosa, Rupert Abele, Marie Jose Abi Saad, Caterina Alfano, Fabio C. L. Almeida, Islam Alshamleh, Gisele Cardoso de Amorim, Thomas K. Anderson, Cristiane D. Anobom, Chelsea Anorma, Jasleen Kaur Bains, Adriaan Bax, Martin Blackledge, Julius Blechar, Anja Bockmann, Louis Brigandat, Anna Bula, Matthias Buetikofer, Aldo R. Camacho-Zarco, Teresa Carlomagno, Icaro Putinhon Caruso, Betul Ceylan, Apirat Chaikuad, Feixia Chu, Laura Cole, Marquise G. Crosby, Vanessa de Jesus, Karthikeyan Dhamotharan, Isabella C. Felli, Jan Ferner, Yanick Fleischmann, Marie-Laure Fogeron, Nikolaos K. Fourkiotis, Christin Fuks, Boris Fuertig, Angelo Gallo, Santosh L. Gande, Juan Atilio Gerez, Dhiman Ghosh, Francisco Gomes-Neto, Oksana Gorbatyuk, Serafima Guseva, Carolin Hacker, Sabine Haefner, Bing Hao, Bruno Hargittay, K. Henzler-Wildman, Jeffrey C. Hoch, Katharina F. Hohmann, Marie T. Hutchison, Kristaps Jaudzems, Katarina Jovic, Janina Kaderli, Gints Kalnins, Iveta Kanepe, Robert N. Kirchdoerfer, John Kirkpatrick, Stefan Knapp, Robin Krishnathas, Felicitas Kutz, Susanne zur Lage, Roderick Lambertz, Andras Lang, Douglas Laurents, Lauriane Lecoq, Verena Linhard, Frank Loehr, Anas Malki, Luiza Mamigonian Bessa, Rachel W. Martin, Tobias Matzel, Damien Maurin, Seth W. McNutt, Nathane Cunha Mebus-Antunes, Beat H. Meier, Nathalie Meiser, Miguel Mompean, Elisa Monaca, Roland Montserret, Laura Marino Perez, Celine Moser, Claudia Muhle-Goll, Thais Cristtina Neves-Martins, Xiamonin Ni, Brenna Norton-Baker, Roberta Pierattelli, Letizia Pontoriero, Yulia Pustovalova, Oliver Ohlenschlaeger, Julien Orts, Andrea T. Da Poian, Dennis J. Pyper, Christian Richter, Roland Riek, Chad M. Rienstra, Angus Robertson, Anderson S. Pinheiro, Raffaele Sabbatella, Nicola Salvi, Krishna Saxena, Linda Schulte, Marco Schiavina, Harald Schwalbe, Mara Silber, Marcius da Silva Almeida, Marc A. Sprague-Piercy, Georgios A. Spyroulias, Sridhar Sreeramulu, Jan-Niklas Tants, Kaspars Tars, Felix Torres, Sabrina Toews, Miguel A. Trevino, Sven Trucks, Aikaterini C. Tsika, Krisztina Varga, Ying Wang, Marco E. Weber, Julia E. Weigand, Christoph Wiedemann, Julia Wirmer-Bartoschek, Maria Alexandra Wirtz Martin, Johannes Zehnder, Martin Hengesbach, Andreas Schlundt

Summary: The international COVID19-NMR consortium aims to gather scientific expertise worldwide to provide new approaches for understanding the molecular components of SARS-CoV-2. By making viral proteins and RNAs available, the consortium accelerates research on the virus and provides protocols for large-scale production. The NMR investigations and resources disclosed through the consortium offer valuable insights and tools for further studies on SARS-CoV-2.

FRONTIERS IN MOLECULAR BIOSCIENCES (2021)

Article Chemistry, Multidisciplinary

Identification of RNA Base Pairs and Complete Assignment of Nucleobase Resonances by Proton-Detected Solid-State NMR Spectroscopy at 100 kHz MAS

Philipp Innig Aguion, John Kirkpatrick, Teresa Carlomagno, Alexander Marchanka

Summary: Knowledge of RNA structure, whether in isolation or in complex, is crucial for understanding cellular processes. Solid-state NMR has been used to study high molecular-weight complexes, and recent developments in H-1 detection at fast MAS rates have overcome sensitivity and resolution limitations, allowing for more efficient analysis of RNA structures in protein-RNA complexes of any size.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2021)

Article Multidisciplinary Sciences

Eukaryotic Box C/D methylation machinery has two non-symmetric protein assembly sites

Simone Hoefler, Peer Lukat, Wulf Blankenfeldt, Teresa Carlomagno

Summary: The study found that more than 80% of yeast guide RNAs lack functional box C'/D' motifs, suggesting that eukaryotic Box C/D RNPs have two non-symmetric protein assembly sites and their three-dimensional architecture differs from that of archaeal 2'-O-methylation enzymes.

SCIENTIFIC REPORTS (2021)

Article Microbiology

Recruitment of phospholipase Cγ1 to the non-structural membrane protein pK15 of Kaposi Sarcoma-associated herpesvirus promotes its Src-dependent phosphorylation

Naira Samarina, George Ssebyatika, Tanvi Tikla, Ja-Yun Waldmann, Bizunesh Abere, Vittoria Nanna, Michelangelo Marasco, Teresa Carlomagno, Thomas Krey, Thomas F. Schulz

Summary: The interaction between KSHV infection-induced Kaposi's sarcoma and PLCγ1 structure provides a new clue for potential drug targets. pK15 is considered to be a gene that promotes PLCγ1 activation, which can be inhibited from binding to PLCγ1 by drugs.

PLOS PATHOGENS (2021)

Article Biochemistry & Molecular Biology

Nucleic acid-protein interfaces studied by MAS solid-state NMR spectroscopy

Philipp Innig Aguion, Alexander Marchanka, Teresa Carlomagno

Summary: Solid-state NMR (ssNMR) has emerged as a crucial technique for investigating large and insoluble protein assemblies, but its application to nucleic acid-protein complexes has been limited. Recent advancements have led to the first structure determination of an RNA molecule using ssNMR, and new methodologies have been developed to probe nucleic acid-protein interfaces.

JOURNAL OF STRUCTURAL BIOLOGY-X (2022)

Article Biochemistry & Molecular Biology

Structural insights into the activity regulation of full-length non-structural protein 1 from SARS-CoV-2

Ying Wang, John Kirkpatrick, Susanne zur Lage, Teresa Carlomagno

Summary: Non-structural protein 1 (Nsp1) of SARS-CoV-2 is a key virulence factor and potential drug target. The structure of full-length Nsp1 reveals an a/b fold with a globular N-terminal domain (NTD) and flexible tails. The NTD plays a critical role in viral mRNA recognition and gene expression. The interaction between the folded NTD and disordered C-terminal region regulates Nsp1 activity, providing insights for drug design targeting Nsp1.

STRUCTURE (2023)

Article Biochemical Research Methods

A real-time analysis of GFP unfolding by the AAA plus unfoldase PAN

Georg Krueger, John Kirkpatrick, Emilie Mahieu, Bruno Franzetti, Frank Gabel, Teresa Carlomagno

Summary: Protein quality control systems are essential for maintaining a healthy proteome. They eliminate misfolded proteins and regulate protein levels in response to environmental changes. However, the fate of substrates during the unfolding and proteolytic processes is still poorly understood.

JOURNAL OF MAGNETIC RESONANCE (2023)

Article Biochemistry & Molecular Biology

An NMR Study of a 300-kDa AAA+ Unfoldase

Georg Krueger, John Kirkpatrick, Emilie Mahieu, Bruno Franzetti, Frank Gabel, Teresa Carlomagno

Summary: AAA+ ATPases are hexameric unfoldases involved in protein quality control in cells. They, together with proteases, form a protein degradation machinery called the proteasome in archaea and eukaryotes. Using solution-state NMR spectroscopy, this study determined the symmetry properties of the archaeal PAN AAA+ unfoldase and provided insights into its functional mechanism. The study revealed that PAN assembles into a hexamer with C2 symmetry and proposed that archaeal ATPases are flexible enzymes that can adopt distinct conformations. The findings highlight the importance of studying dynamic systems in solution.

JOURNAL OF MOLECULAR BIOLOGY (2023)

Article Biochemistry & Molecular Biology

The EJC disassembly factor PYM is an intrinsically disordered protein and forms a fuzzy complex with RNA

Deepshikha Verma, Veena Hegde, John Kirkpatrick, Teresa Carlomagno

Summary: The discovery of a fuzzy protein-RNA complex formed by the intrinsically unfolded protein PYM and RNA suggests that specific interactions can occur without well-defined intermolecular interfaces. The first 160 amino acids of PYM (PYM1-160) were shown to be intrinsically disordered and capable of binding RNA independently of its nucleotide sequence. This fuzzy protein-RNA complex down-regulates PYM activity by blocking its interaction with the exon junction complex (EJC), thus enabling PYM to bind to a variety of diverse interaction partners.

FRONTIERS IN MOLECULAR BIOSCIENCES (2023)

Article Chemistry, Multidisciplinary

Experiment-guided molecular simulations define a heterogeneous structural ensemble for the PTPN11 tandem SH2 domains

Michelangelo Marasco, John Kirkpatrick, Teresa Carlomagno, Jochen S. Hub, Massimiliano Anselmi

Summary: SHP2 is a critical protein involved in regulating cellular processes, and its mutations can lead to developmental disorders and cancer. The protein consists of multiple domains, including two SH2 domains and a catalytic PTP domain. The relative orientation and spacing between the SH2 domains play a crucial role in enzymatic activation. Previous studies have not provided a clear picture of the SH2 domain structure, but experiment-guided molecular simulations have revealed the structural flexibility of the tandem SH2 in solution, suggesting its importance in SHP2's functional activity.

CHEMICAL SCIENCE (2023)

Article Biochemistry & Molecular Biology

Phosphotyrosine couples peptide binding and SHP2 activation via a dynamic allosteric network

Michelangelo Marasco, John Kirkpatrick, Vittoria Nanna, Justyna Sikorska, Teresa Carlomagno

Summary: SHP2 is a widely distributed protein tyrosine phosphatase whose activity is regulated by phosphotyrosine-containing peptides generated in response to extracellular stimuli. The essential role of phosphotyrosine in regulating SHP2 activity involves enhancing dynamics of the N-SH2 EF and BG loops via an allosteric communication network, leading to destabilization of the N-SH2-PTP interaction surface. This allows for enhanced binding of phosphopeptides and subsequent stabilization of activated SHP2.

COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL (2021)

No Data Available