ArticleThe Biochemical journal2014
Structure of cyclin G-associated kinase (GAK) trapped in different conformations using nanobodies.
Article in The Biochemical journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
32 citing papers in PubMed, 69 citations in OpenAlex.
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- Site-Specific Competitive Kinase Inhibitor Target Profiling Using Phosphonate Affinity Tags.Molecular & cellular proteomics : MCP · 2025Article
- From discovery to treatment: tracing the path of hepatitis E virus.Virology journal · 2024Review
- A designed ankyrin-repeat protein that targets Parkinson's disease-associated LRRK2.The Journal of biological chemistry · 2024Article
- Nanobodies in the fight against infectious diseases: repurposing nature's tiny weapons.World journal of microbiology & biotechnology · 2024Review
- Synthesis of a 3,7-Disubstituted Isothiazolo[4,3-Molecules (Basel, Switzerland) · 2024Article
- Recent progress in discovery of novel AAK1 inhibitors: from pain therapy to potential anti-viral agents.Journal of enzyme inhibition and medicinal chemistry · 2023Review
- VHH CDR-H3 conformation is determined by VH germline usage.Communications biology · 2023Article
- Quantitative flow cytometric selection of tau conformational nanobodies specific for pathological aggregates.Frontiers in immunology · 2023Article
- Genome- and Exome-Wide Association Studies Revealed Candidate Genes Associated with DaTscan Imaging Features.Parkinson's disease · 2023Article
- Oral antiviral treatments for COVID-19: opportunities and challenges.Pharmacological reports : PR · 2022Review
- Structural Insight into TNIK Inhibition.International journal of molecular sciences · 2022Review
- Micro RNAs-The Small Big Players in Hepatitis E Virus Infection: A Comprehensive Review.Biomolecules · 2022Review
- Aurora Kinase A Is Involved in Controlling the Localization of Aquaporin-2 in Renal Principal Cells.International journal of molecular sciences · 2022Article
- Roles of existing drug and drug targets for COVID-19 management.Metabolism open · 2021Article
- Milk Peptides as Novel Multi-Targeted Therapeutic Candidates for SARS-CoV2.The protein journal · 2021Article
- Allosteric inhibition of LRRK2, where are we now.Biochemical Society transactions · 2020Review
- Chemogenetic Control of Nanobodies.Nature methods · 2020Article
- Towards the Development of an In vivo Chemical Probe for Cyclin G Associated Kinase (GAK).Molecules (Basel, Switzerland) · 2019Article
- DNAJC proteins and pathways to parkinsonism.The FEBS journal · 2019Review
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
GAK (cyclin G-associated kinase) is a key regulator of clathrin-coated vesicle trafficking and plays a central role during development. Additionally, due to the unusually high plasticity of its catalytic domain, it is a frequent 'off-target' of clinical kinase inhibitors associated with respiratory side effects of these drugs. In the present paper, we determined the crystal structure of the GAK catalytic domain alone and in complex with specific single-chain antibodies (nanobodies). GAK is constitutively active and weakly associates in solution. The GAK apo structure revealed a dimeric inactive state of the catalytic domain mediated by an unusual activation segment interaction. Co-crystallization with the nanobody NbGAK_4 trapped GAK in a dimeric arrangement similar to the one observed in the apo structure, whereas NbGAK_1 captured the activation segment of monomeric GAK in a well-ordered conformation, representing features of the active kinase. The presented structural and biochemical data provide insight into the domain plasticity of GAK and demonstrate the utility of nanobodies to gain insight into conformational changes of dynamic molecules. In addition, we present structural data on the binding mode of ATP mimetic inhibitors and enzyme kinetic data, which will support rational inhibitor design of inhibitors to reduce the off-target effect on GAK.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.