Crystal Structure of Mistletoe Lectin I (ML-I) from Viscum album in Complex with 4-N-Furfurylcytosine at 2.85 Å Resolution

Ahmad, Malik Shoaib; Rasheed, Saima; Khaliq, Binish; Perbandt, Markus; Choudhary, Muhammad Iqbal; Markiewicz, Wojciech T.; Barciszewski, Jan; Betzel, Christian

doi:10.2174/1573406414666180524095946

Cited by 9 publications

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“…Lectins are well-known for their capacity of linkage to the sugar component of membrane cells (the name derives from the Latin word lego , meaning “to link”). The biochemistry and structures of three types of V. album lectins were studied and characterized, termed mistletoelectins I, II and III (MLI, MLII and MLIII) [ 61 , 62 , 63 ], evidencing their role as precursors to proteins and the structures based on two chains, post-translationally cleaved into an alpha and a beta chain. The two chains are stabilized by linkage via disulfide bridges [ 64 ].…”

Section: Introductionmentioning

confidence: 99%

The Anti-Inflammatory Activity of Viscum album

Nicoletti

2023

Plants

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The therapeutic story of European mistletoe (Viscum album L.) presents a seesawing profile. In ancient times, this hemiparasitic plant was considered a panacea and even to be endowed with exceptional beneficial properties. In more recent times, despite its multiple uses in traditional medicines, some parts of the plant, in particular the berries, were considered poisonous and dangerous, including concerns of cytotoxicity, which spread serious suspicion on its medicinal utility. However, since the last century, medical interest in mistletoe has come back in force due to its utilization in clinical cancer treatments, based on its selective action on tumor cells. In Central Europe, the hydro-alcoholic extracts of European mistletoe register a relevant and continuous utilization in anthroposophic medicine, which is a holistic system that includes the utilization of phytomedicinal substances. In Switzerland and Germany, most physicians and patients use these products as complementary therapy in oncological treatments. However, despite its increasing use in this field, the results of mistletoe’s use are not always convincing, and other aspects have appeared. Nowadays, products that contain mistletoe are utilized in several fields, including diet, phytotherapy, veterinary medicine and homeopathy, but in particular in cancer therapies as coadjuvant factors, in consideration of several positive effects including effects in the improvement of quality-of-life conditions and reinforcement of the immune system. In this review, based on the understanding of the association between cancer and inflammation, we propose a relationship between these recent uses of mistletoe, based on its antioxidant properties, which are supported by phytochemical and pharmacological data. The unicity of mistletoe metabolism, which is a direct consequence of its hemiparasitism, is utilized as a key interpretation element to explain its biological properties and steer its consequent therapeutic uses.

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Section: Introductionmentioning

confidence: 99%

The Anti-Inflammatory Activity of Viscum album

Nicoletti

2023

Plants

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“…Five invariant residues Y74, Y113, E164, R167, and W198 are present at the active site of ABA and are known to be conserved throughout wide range of RIPs . The final 2mFo‐DFc electron density map contoured at 1.0σ‐level for apo‐ABA crystal structure shows well‐defined electron density for the active site residues and two distinct conformations of active site Y74 (Fig.…”

Section: Resultsmentioning

confidence: 96%

Structural basis for neutralization of cytotoxic abrin by monoclonal antibody D6F10

et al. 2019

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Abrin, an extremely cytotoxic Type II ribosome‐inactivating protein (RIP), is a potential bio‐warfare agent. Abrin A‐chain (ABA) depurinates an adenosine of sarcin‐ricin loop (SRL) from eukaryotic 28S rRNA, thereby arresting protein synthesis and leading to cell death. Monoclonal antibody (mAb) D6F10 is the only known antibody that neutralizes ABA's activity in cell‐free systems as well as abrin's toxicity in vitro and in vivo. However, how binding of mAb D6F10 to abrin interferes with abrin's catalytic activity at ribosome is still poorly understood. To provide structural basis for mAb D6F10‐mediated rescue of ribosome inactivation by abrin, we determined crystal structures of ABA with and without substrate analogs. The structures of ABA‐substrate analogs and ribosome were used in an experiment‐guided computational protocol, to construct the ABA‐Ribosome complex. A homology model of the variable region (Fv) of mAb D6F10 was generated and docked with the apo‐ABA structure to construct the ABA‐D6F10 Fv complex. Structural superposition of ABA common to ABA‐D6F10 Fv and ABA‐Ribosome complexes reveals steric hindrance as the primary mechanism by which mAb D6F10 neutralizes abrin. In contrast to ABA alone, ABA bound to mAb D6F10 is unable to access the SRL on the ribosome owing to steric clashes of mAb D6F10 with the ribosome. Crystal structures of ABA also reveal a catalytic water molecule implicated in hydrolyzing N‐glycosidic bond of the susceptible adenosine by RIPs. Furthermore, our strategy provides structural details of steric hindrance important for neutralization of ricin, another RIP, by mAb 6C2 and hence is of wide applicability. Enzyme http://www.chem.qmul.ac.uk/iubmb/enzyme/EC3/2/2/22.html. Database Structural data have been deposited in the Protein Data Bank (PDB) under the accession numbers http://www.rcsb.org/pdb/search/structidSearch.do?structureId=5Z37, http://www.rcsb.org/pdb/search/structidSearch.do?structureId=5Z3I, and http://www.rcsb.org/pdb/search/structidSearch.do?structureId=5Z3J.

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“…A1, A2, A3 and A4, with A3 being the predominant isoform ( Majeed and Rehman, 2021 ; Yousefvand et al, 2022 ; Zhang et al, 2022 ). Moreover, three types of lectins (termed mistletoelectins I, II, and III) have been identified in V. album L. ( Yousefvand et al, 2022 ; Niwa et al, 2003 ; Ahmad et al, 2018 ; Szurpnicka et al, 2019 ; Szurpnicka et al, 2020 ; de Almeida et al, 2023 ; Nicoletti, 2023a ). The chemical content of V. album L. and other mistletoe species are described in Figure 1 .…”

Section: Chemical Content Of Mistletoementioning

confidence: 99%

The cardioprotective potential of selected species of mistletoe

Olas

2024

Front. Pharmacol.

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Mistletoe is an evergreen woody shrub with stems measuring 30–100 cm. It has leathery, yellowish-green strap-shaped leaves, yellowish-green flowers, and bears typical berries. The most common species is Viscum album L., mainly present in Europe and Asia. It is commonly known as European mistletoe or simply, mistletoe. Scientific interest in mistletoe was awakened in the XX century. Mistletoe, especially V. album L., has historically been used in the treatment and prophylaxis of CVD, with its properties being confirmed in recent studies. This mini-review describes new aspects of the cardioprotective properties of various species of mistletoe, especially V. album L. The effect of oral and subcutaneous application of fresh V. album L. extracts on blood pressure has been studied in various models; while the data suggests that mistletoe may be a promising herbal extract with cardioprotective properties, the species has only been tested in vitro and in vivo, on animals. In addition, it is unclear whether the cardioprotective activity of mistletoe may be due to particular chemical components, as the chemical composition of mistletoe extracts can vary depending on inter alia the time of harvest, extraction method and plant part. Hence, this activity may instead result from synergistic interactions between various secondary metabolites. Therefore, further studies are needed to identify the mechanisms of action of mistletoe compounds on CVDs, and determine their interactions with other cardioprotective drugs, their metabolic mechanisms, pharamacokinetics and adverse effects. More research is also needed to determine the therapeutic doses of active ingredients for use in clinical trials; this would require an accurate understanding of the chemical composition of extracts from different species of mistletoe (not only V. album L.) and from various host trees.

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Crystal Structure of Mistletoe Lectin I (ML-I) from Viscum album in Complex with 4-N-Furfurylcytosine at 2.85 Å Resolution

Cited by 9 publications

References 0 publications

The Anti-Inflammatory Activity of Viscum album

The Anti-Inflammatory Activity of Viscum album

Structural basis for neutralization of cytotoxic abrin by monoclonal antibody D6F10

The cardioprotective potential of selected species of mistletoe

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