4,158 results match your criteria bind pocket

Cytotoxicity, anti-angiogenic, anti-tumor and molecular docking studies on phytochemicals isolated from Polygonum hydropiper L.

BMC Complement Med Ther 2021 Sep 24;21(1):239. Epub 2021 Sep 24.

Department of Pharmacy, Faculty of Biological Sciences, University of Malakand, Chakdara, 18000 Dir (L), KP, Pakistan.

Background: According to the recent global cancer statistics, breast cancer is the leading cause of deaths among women with 2.3 million new cases globally. Likewise, cervical cancer is also among the leading causes of mortality among women. Read More

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September 2021

Structural study of AAVrh.10 Receptor and Antibody Interactions.

J Virol 2021 Sep 22:JVI0124921. Epub 2021 Sep 22.

Department of Biochemistry and Molecular Biology, Center for Structural Biology, McKnight Brain Institute, College of Medicine, University of Florida, Gainesville, Florida, USA.

Recombinant Adeno-associated virus (rAAV) vectors are one of the leading tools for the delivery of therapeutic genes in human gene therapy applications. For a successful transfer of their payload, the AAV vectors have to circumvent potential pre-existing neutralizing host antibodies and bind to the receptor of the target cells. Both these aspects have not been structurally analyzed for AAVrh. Read More

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September 2021

and studies of holothurin A on androgen receptor in prostate cancer.

J Biomol Struct Dyn 2021 Sep 13:1-9. Epub 2021 Sep 13.

Department of Pharmaceutical Chemistry, Faculty of Life Sciences, University of Vienna, Vienna, Austria.

The androgen receptor (AR) plays a crucial role in the growth of prostate cancer, and has long been considered the cancer's primary strategic therapeutic target. However, despite the early susceptibility, patients receiving hormonal therapy targeting AR are likely to develops resistance to the treatment and progresses to the castration-resistant stage as a consequence of the mutation at the ligand binding pocket of AR. Interestingly, the surface pocket of the AR called binding function 3 (BF3) has been reported as a great benefit for treating a recurrent tumor. Read More

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September 2021

SAR of novel benzothiazoles targeting an allosteric pocket of DENV and ZIKV NS2B/NS3 proteases.

Bioorg Med Chem 2021 Sep 4;47:116392. Epub 2021 Sep 4.

Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg-University, Staudingerweg 5, 55128 Mainz, Germany. Electronic address:

In recent years, dengue virus (DENV) and Zika virus (ZIKV), both mosquito-borne members of the Flaviviridae family, have emerged as intercontinental health issues since their vectors have spread from their tropical origins to temperate climate zones due to climate change and increasing globalization. DENV and ZIKV are positive-sense, single-stranded RNA viruses, whose genomes consist of three structural (capsid, membrane precursor, envelope) and seven non-structural (NS) proteins, all of which are initially expressed as a single precursor polyprotein. For virus maturation, the polyprotein processing is accomplished by host proteases and the viral NS2B/NS3 protease complex, whose inhibitors have been shown to be effective antiviral agents with loss of viral pathogenicity. Read More

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September 2021

Discovery of a cryptic site at the interface 2 of TEAD - Towards a new family of YAP/TAZ-TEAD inhibitors.

Eur J Med Chem 2021 Sep 6;226:113835. Epub 2021 Sep 6.

Univ Lille, INSERM, CHU Lille, UMR-S 1172, Lille Neuroscience and Cognition Research Center, F-59000, Lille, France; ENSCL-Centrale Lille, CS 90108, F-59652, Villeneuve d'Ascq Cedex, France. Electronic address:

The Hippo pathway is involved in organ size control and tissue homeostasis by regulating cell growth, proliferation and apoptosis. It controls the phosphorylation of the transcription co-activator YAP (Yes associated protein) and TAZ (Transcriptional coactivator with PDZ-binding motif) in order to control their nuclear import and their interaction with TEAD (Transcriptional Enhanced Associated Domain). YAP, TAZ and TEADs are dysregulated in several cancers making YAP/TAZ-TEAD interaction a new emerging anti-cancer target. Read More

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September 2021

Involvement of Chemosensory Protein BodoCSP1 in Perception of Host Plant Volatiles in .

J Agric Food Chem 2021 Sep 10;69(37):10797-10806. Epub 2021 Sep 10.

State Key Laboratory of Crop Stress Biology for Arid Areas, and Key Laboratory of Plant Protection Resources and Pest Management of the Ministry of Education, College of Plant Protection, Northwest A&F University, Yangling 712100, Shaanxi, China.

Chemosensory proteins (CSPs) can bind and transport odorant molecules and play important roles in insect chemoreception. In this study, we focused on the roles of a chemosensory protein (BodoCSP1) in perception of host plant volatiles in . The expression of was significantly higher in adults than in larvae and pupae, without a significant difference between male and female adults. Read More

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September 2021

Insights into small molecule inhibitor bindings to PD-L1 with residue-specific binding free energy calculation.

J Biomol Struct Dyn 2021 Sep 6:1-9. Epub 2021 Sep 6.

Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, Shanghai Key Laboratory of Green Chemistry & Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, China.

Targeting the immunological checkpoint PD-1/PD-L1 with antibodies has shown opportunities to improve cancer treatment in recent years. However, antibody therapy is a double-edged sword with high cost, low patient tolerance, lack of oral bioavailability, and a reaction to most solid tumors that prevents the adoption of antibodies. Advancement of small-molecule PD-1/PD-L1 inhibitors that could overwhelm these drawbacks is sluggish because of the poor pharmacodynamic properties and shallow pocket of the PD-1/PD-L1 binding interface. Read More

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September 2021

A Water Soluble Pd L Cage for Selective Binding of Neu5Ac.

Chemistry 2021 Sep 6. Epub 2021 Sep 6.

Van 't Hoff Institute for Molecular Sciences, University of Amsterdam, Science Park 904, 1098 XH, Amsterdam (The, Netherlands.

The sialic acid N-acetylneuraminic acid (Neu5Ac) and its derivatives are involved in many biological processes including cell-cell recognition and infection by influenza. Molecules that can recognize Neu5Ac might thus be exploited to intervene in or monitor such events. A key obstacle in this development is the sparse availability of easily prepared molecules that bind to this carbohydrate in its natural solvent; water. Read More

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September 2021

Binding specificity and function of the SWI/SNF subunit SMARCA4 bromodomain interaction with acetylated histone H3K14.

J Biol Chem 2021 Aug 30:101145. Epub 2021 Aug 30.

Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC, 27695-7622, USA. Electronic address:

Bromodomains (BD) are conserved reader modules that bind acetylated lysine residues on histones. Although much has been learned regarding the in vitro properties of these domains, less is known about their function within chromatin complexes. SWI/SNF chromatin-remodeling complexes modulate transcription and contribute to DNA damage repair. Read More

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Frag4Lead: growing crystallographic fragment hits by catalog using fragment-guided template docking.

Acta Crystallogr D Struct Biol 2021 Sep 23;77(Pt 9):1168-1182. Epub 2021 Aug 23.

Macromolecular Crystallography, Helmholtz-Zentrum Berlin, Albert-Einstein-Straße 15, D-12489 Berlin, Germany.

In recent years, crystallographic fragment screening has matured into an almost routine experiment at several modern synchrotron sites. The hits of the screening experiment, i.e. Read More

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September 2021

How phosphorylation of peptides affects their interaction with 14-3-3η domains.

Proteins 2021 Aug 30. Epub 2021 Aug 30.

Center for Bioinformatics, Saarland University, Saarbrücken, Germany.

Members of the 14-3-3 domain family have important functions as adapter domains. Via an amphipathic groove on their protein surface they typically bind to disordered C-terminals of other proteins. Importantly, binding partners of 14-3-3 domains usually contain a phosphorylated serine or threonine residue at their binding interface and possess one of three different sequence motifs. Read More

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A novel and efficient approach to high-throughput production of HLA-E/peptide monomer for T-cell epitope screening.

Sci Rep 2021 08 26;11(1):17234. Epub 2021 Aug 26.

P2R "Production de Protéines Recombinantes", Université de Nantes, CRCINA, SFR-Santé, INSERM, CNRS, CHU Nantes, Nantes, France.

Over the past two decades, there has been a great interest in the study of HLA-E-restricted αβ T cells during bacterial and viral infections, including recently SARS-CoV-2 infection. Phenotyping of these specific HLA-E-restricted T cells requires new tools such as tetramers for rapid cell staining or sorting, as well as for the identification of new peptides capable to bind to the HLA-E pocket. To this aim, we have developed an optimal photosensitive peptide to generate stable HLA-E/pUV complexes allowing high-throughput production of new HLA-E/peptide complexes by peptide exchange. Read More

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Role of substrate recognition in modulating strigolactone receptor selectivity in witchweed.

J Biol Chem 2021 Aug 23:101092. Epub 2021 Aug 23.

Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, IL 61801; Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, IL 61801; National Center for Supercomputing Applications, University of Illinois at Urbana-Champaign, Urbana, IL 61801; Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, Urbana, IL 61801; NIH Center for Macromolecular Modeling and Bioinformatics, University of Illinois at Urbana-Champaign, Urbana, IL 61801. Electronic address:

Witchweed, or Striga hermonthica, is a parasitic weed that destroys billions of dollars' worth of crops globally every year. Its germination is stimulated by strigolactones exuded by its host plants. Despite high sequence, structure, and ligand binding site conservation across different plant species, one strigolactone receptor in witchweed, ShHTL7, uniquely exhibits a picomolar EC50 for downstream signaling. Read More

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Virtual screening and biological evaluation of PPARγ antagonists as potential anti-prostate cancer agents.

Bioorg Med Chem 2021 Aug 13;46:116368. Epub 2021 Aug 13.

Department of Chemistry, University of Nebraska at Omaha, 6001 Dodge Street, Omaha, NE 68182, United States. Electronic address:

The peroxisome proliferator-activated receptor gamma (PPARγ) was identified as an oncogene and it plays a key role in prostate cancer (PC) development and progression. PPARγ antagonists have been shown to inhibit PC cell growth. Herein, we describe a virtual screening-based approach that led to the discovery of novel PPARγ antagonist chemotypes that bind at the allosteric pocket. Read More

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Application of ensemble pharmacophore-based virtual screening to the discovery of novel antimitotic tubulin inhibitors.

Comput Struct Biotechnol J 2021 3;19:4360-4372. Epub 2021 Aug 3.

Laboratorio de Química Orgánica y Farmacéutica, Departamento de Ciencias Farmacéuticas, Facultad de Farmacia, Universidad de Salamanca, Salamanca, Spain.

Tubulin is a well-validated target for herbicides, fungicides, anti-parasitic, and anti-tumor drugs. Many of the non-cancer tubulin drugs bind to its colchicine site but no colchicine-site anticancer drug is available. The colchicine site is composed of three interconnected sub-pockets that fit their ligands and modify others' preference, making the design of molecular hybrids (that bind to more than one sub-pocket) a difficult task. Read More

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Venetoclax: a promising repurposed drug against SARS-CoV-2 main protease.

J Biomol Struct Dyn 2021 Aug 23:1-12. Epub 2021 Aug 23.

Department of Chemistry, Indian Institute of Technology Guwahati, Guwahati, India.

Global health care emergency caused by a new coronavirus (severe acute respiratory syndrome coronavirus 2 or SARS-CoV-2) demands urgent need to repurpose the approved pharmaceutical drugs. Main protease, M of SARS-CoV-2 draws significant attention as a drug target. Herein, we have screened FDA approved organosulfur drugs (till 2016) and our laboratory synthesized organosulfur and organoselenium compounds (L1-L306) against M-apo using docking followed by classical MD simulations. Read More

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Cannabinoid receptor interacting protein 1a interacts with myristoylated Gα N terminus via a unique gapped β-barrel structure.

J Biol Chem 2021 Aug 19;297(3):101099. Epub 2021 Aug 19.

Department of Biochemistry and Center for Structural Biology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA; Center for Molecular Signaling, Wake Forest University, Winston-Salem, North Carolina, USA. Electronic address:

Cannabinoid receptor interacting protein 1a (CRIP1a) modulates CB cannabinoid receptor G-protein coupling in part by altering the selectivity for Gα subtype activation, but the molecular basis for this function of CRIP1a is not known. We report herein the first structure of CRIP1a at a resolution of 1.55 Å. Read More

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Oligomerization-Enhanced Receptor-Ligand Binding Revealed by Dual-Color Simultaneous Tracking on Living Cell Membranes.

J Phys Chem Lett 2021 Sep 19;12(34):8164-8169. Epub 2021 Aug 19.

State Key Laboratory of Heavy Oil Processing and Center for Bioengineering and Biotechnology, China University of Petroleum (East China), Qingdao 266580, P. R. China.

GPCR oligomerization plays a critical role in cellular signaling, yet the stoichiometry of the interactions between oligomers and binding ligands in living cells remains a longstanding challenge. Here, by developing a dual-color simultaneous tracking system based on a total internal reflection fluorescence microscope (TIRFM), the CCR5-CCL5 interactions are visualized and quantitatively assessed in real time. Results show that each oligomeric state of CCR5 could bind with CCL5 but with different binding affinities; CCR5 dimers have a 3. Read More

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September 2021

Nicotinic acid mononucleotide is an allosteric SARM1 inhibitor promoting axonal protection.

Exp Neurol 2021 Nov 14;345:113842. Epub 2021 Aug 14.

Washington University School of Medicine in Saint Louis, Department of Genetics, St. Louis, MO, USA; Needleman Center for Neurometabolism and Axonal Therapeutics, USA.

SARM1 is an inducible NAD hydrolase that is the central executioner of pathological axon loss. Recently, we elucidated the molecular mechanism of SARM1 activation, demonstrating that SARM1 is a metabolic sensor regulated by the levels of NAD and its precursor, nicotinamide mononucleotide (NMN), via their competitive binding to an allosteric site within the SARM1 N-terminal ARM domain. In healthy neurons with abundant NAD, binding of NAD blocks access of NMN to this allosteric site. Read More

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November 2021

Molecular mechanisms of the anti-cancer drug, LY2874455, in overcoming the FGFR4 mutation-based resistance.

Sci Rep 2021 Aug 16;11(1):16593. Epub 2021 Aug 16.

Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran.

In recent years, many strategies have been used to overcome the fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitors (TKIs) resistance caused by different mutations. LY2874455 (or 6LF) is a pan-FGFR inhibitor which is identified as the most efficient TKI for all resistant mutations in FGFRs. Here, we perform a comparative dynamics study of wild type (WT) and the FGFR4 V550L mutant for better understanding of the 6LF inhibition mechanism. Read More

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Zinc thiotropolone combinations as inhibitors of the SARS-CoV-2 main protease.

Dalton Trans 2021 Sep 14;50(35):12226-12233. Epub 2021 Sep 14.

3255 TAMU, College Station, TX, 77843, USA.

Numerous organic molecules are known to inhibit the main protease of SARS-CoV-2, (SC2M), a key component in viral replication of the 2019 novel coronavirus. We explore the hypothesis that zinc ions, , bind to the SC2M enzyme in combination with lipophilic tropolone and thiotropolone ligands, , block substrate docking, and inhibit function. This study combines synthetic inorganic chemistry, protease activity assays, and computational modeling. Read More

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September 2021

On the Mechanism of Alkylammonium Ligands Binding to the Surface of CsPbBr Nanocrystals.

Chem Mater 2021 Aug 21;33(15):5962-5973. Epub 2021 Jun 21.

Laboratory of Inorganic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zürich, Vladimir Prelog Weg 1, CH-8093 Zürich, Switzerland.

CsPbBr nanocrystals (NCs) suffer from instabilities caused by the dynamic and labile nature of both the inorganic core and the organic-inorganic interface. Surface ligand engineering thus remains an imminent research topic. In this study, classical molecular dynamics simulations with an explicit solvent are used to gain insights into the inherent binding properties of three different alkylammonium ligands-primary dodecylammonium (DA), secondary didodecylammonium (DDA), and quaternary dimethyldi- dodecylammonium (DMDDA). Read More

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Structural basis of bilin binding by the chlorophyll biosynthesis regulator GUN4.

Protein Sci 2021 Oct 21;30(10):2083-2091. Epub 2021 Aug 21.

School of Life Sciences, Anhui University, Hefei, China.

The chlorophyll biosynthesis regulator GENOMES UNCOUPLED 4 (GUN4) is conserved in nearly all oxygenic photosynthetic organisms. Recently, GUN4 has been found to be able to bind the linear tetrapyrroles (bilins) and stimulate the magnesium chelatase activity in the unicellular green alga Chlamydomonas reinhardtii. Here, we characterize GUN4 proteins from Arabidopsis thaliana and the cyanobacterium Synechocystis sp. Read More

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October 2021

A fragment-based approach identifies an allosteric pocket that impacts malate dehydrogenase activity.

Commun Biol 2021 08 10;4(1):949. Epub 2021 Aug 10.

Drug Design, University of Groningen, Department of Pharmacy, Groningen, The Netherlands.

Malate dehydrogenases (MDHs) sustain tumor growth and carbon metabolism by pathogens including Plasmodium falciparum. However, clinical success of MDH inhibitors is absent, as current small molecule approaches targeting the active site are unselective. The presence of an allosteric binding site at oligomeric interface allows the development of more specific inhibitors. Read More

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Molecular Mechanism of Inhibiting WNK Binding to OSR1 by Targeting the Allosteric Pocket of the OSR1-CCT Domain with Potential Antihypertensive Inhibitors: An Study.

J Phys Chem B 2021 Aug 9;125(32):9115-9129. Epub 2021 Aug 9.

Department of Biosciences and Biomedical Engineering, Indian Institute of Technology Indore, Khandwa Road, Indore, Madhya Pradesh 453552, India.

The oxidative-stress-responsive kinase 1 (OSR1) and the STE20/SPS1-related proline-alanine-rich kinase (SPAK) are physiological substrates of the with-no-lysine (WNK) kinase. They are the master regulators of cation Cl cotransporters that could be targeted for discovering novel antihypertensive agents. Both kinases have a conserved carboxy-terminal (CCT) domain that recognizes a unique peptide motif (Arg-Phe-Xaa-Val) present in their upstream kinases and downstream substrates. Read More

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N1 neuraminidase of H5N1 avian influenza A virus complexed with sialic acid and zanamivir - A study by molecular docking and molecular dynamics simulation.

J Biomol Struct Dyn 2021 Aug 9:1-14. Epub 2021 Aug 9.

Research Laboratory of Molecular Biophysics, Department of Physics, School of Advanced Sciences, Vellore Institute of Technology, Vellore, India.

Development of antiviral drugs is an urgent need to control and prevent the presently circulating H5N1 avian influenza virus which is affects the human respiratory tract. The complex crystal structure of N1-N-acetylneuranamic acid (sialic acid, SIA) is not available as complex and hence SIA and zanamivir (ZMR) are docked into the binding site of N1 neuraminidase. Based on the analysis, the initial complex structures have been simulated for 120 ns to get insight into the binding modes and interaction between protein-ligand complex systems. Read More

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Ribose-Binding Protein Mutants With Improved Interaction Towards the Non-natural Ligand 1,3-Cyclohexanediol.

Front Bioeng Biotechnol 2021 23;9:705534. Epub 2021 Jul 23.

Department of Fundamental Microbiology, University of Lausanne, Lausanne, Switzerland.

Bioreporters consist of genetically modified living organisms that respond to the presence of target chemical compounds by production of an easily measurable signal. The central element in a bioreporter is a sensory protein or aptamer, which, upon ligand binding, modifies expression of the reporter signal protein. A variety of naturally occurring or modified versions of sensory elements has been exploited, but it has proven to be challenging to generate elements that recognize non-natural ligands. Read More

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Conformational dynamics of androgen receptors bound to agonists and antagonists.

Sci Rep 2021 Aug 5;11(1):15887. Epub 2021 Aug 5.

Department of Chemistry and Biochemistry, University of California, Los Angeles, CA, 90095-1569, USA.

The androgen receptor (AR) is critical in the progression of prostate cancer (PCa). Small molecule antagonists that bind to the ligand binding domain (LBD) of the AR have been successful in treating PCa. However, the structural basis by which the AR antagonists manifest their therapeutic efficacy remains unclear, due to the lack of detailed structural information of the AR bound to the antagonists. Read More

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Maturation of the matrix and viral membrane of HIV-1.

Science 2021 08;373(6555):700-704

Department of Infectious Diseases, Virology, Universitätsklinikum Heidelberg, 69120 Heidelberg, Germany.

Gag, the primary structural protein of HIV-1, is recruited to the plasma membrane for virus assembly by its matrix (MA) domain. Gag is subsequently cleaved into its component domains, causing structural maturation to repurpose the virion for cell entry. We determined the structure and arrangement of MA within immature and mature HIV-1 through cryo-electron tomography. Read More

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The 5-formyl-tetrahydrofolate proteome links folates with C/N metabolism and reveals feedback regulation of folate biosynthesis.

Plant Cell 2021 Aug 5. Epub 2021 Aug 5.

CAS Key Laboratory of Synthetic Biology, CAS Center for Excellence in Molecular Plant Sciences, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, Shanghai 200032, China.

Folates are indispensable for plant development, but their molecular mode of action remains elusive. We synthesized a probe, '5-F-THF-Dayne', comprising 5-formyl-tetrahydrofolate coupled to a photoaffinity tag. Exploiting this probe in an affinity proteomics study in Arabidopsis thaliana, we retrieved 51 hits. Read More

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