scholarly journals Crystal structures of peanut lectin in the presence of synthetic β-N- and β-S-galactosides disclose evidence for the recognition of different glycomimetic ligands

2020 ◽  
Vol 76 (11) ◽  
pp. 1080-1091
Author(s):  
Alejandro J. Cagnoni ◽  
Emiliano D. Primo ◽  
Sebastián Klinke ◽  
María E. Cano ◽  
Walter Giordano ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Bacterial Infections ◽  
Carbohydrate Antigen ◽  
Molecular Probes ◽  
Titration Calorimetry ◽  
Peanut Lectin ◽  
Molecular Binding ◽  
The Family ◽  
Inhibition Studies ◽  
Micromolar Range

Carbohydrate–lectin interactions are involved in important cellular recognition processes, including viral and bacterial infections, inflammation and tumor metastasis. Hence, structural studies of lectin–synthetic glycan complexes are essential for understanding lectin-recognition processes and for the further design of promising chemotherapeutics that interfere with sugar–lectin interactions. Plant lectins are excellent models for the study of the molecular-recognition process. Among them, peanut lectin (PNA) is highly relevant in the field of glycobiology because of its specificity for β-galactosides, showing high affinity towards the Thomsen–Friedenreich antigen, a well known tumor-associated carbohydrate antigen. Given this specificity, PNA is one of the most frequently used molecular probes for the recognition of tumor cell-surface O-glycans. Thus, it has been extensively used in glycobiology for inhibition studies with a variety of β-galactoside and β-lactoside ligands. Here, crystal structures of PNA are reported in complex with six novel synthetic hydrolytically stable β-N- and β-S-galactosides. These complexes disclosed key molecular-binding interactions of the different sugars with PNA at the atomic level, revealing the roles of specific water molecules in protein–ligand recognition. Furthermore, binding-affinity studies by isothermal titration calorimetry showed dissociation-constant values in the micromolar range, as well as a positive multivalency effect in terms of affinity in the case of the divalent compounds. Taken together, this work provides a qualitative structural rationale for the upcoming synthesis of optimized glycoclusters designed for the study of lectin-mediated biological processes. The understanding of the recognition of β-N- and β-S-galactosides by PNA represents a benchmark in protein–carbohydrate interactions since they are novel synthetic ligands that do not belong to the family of O-linked glycosides.

scholarly journals Crystal structures of peanut lectin in the presence of synthetic β-N- and β-S-galactosides disclose evidences for the recognition of different glycomimetic ligands

2020 ◽  
Author(s):  
Alejandro J. Cagnoni ◽  
Emiliano D. Primo ◽  
Sebastián Klinke ◽  
María E. Cano ◽  
Walter Giordano ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Bacterial Infections ◽  
Carbohydrate Antigen ◽  
Molecular Probes ◽  
Titration Calorimetry ◽  
Peanut Lectin ◽  
Molecular Binding ◽  
The Family ◽  
Inhibition Studies

AbstractCarbohydrate−lectin interactions are involved in important cellular recognition processes, including viral and bacterial infections, inflammation, and tumor metastasis. Hence, the structural studies of lectin-synthetic glycan complexes are essential for understanding the lectin recognition processes and the further design of promising chemotherapeutics that interfere with sugar-lectin interactions.Plant lectins are excellent models for the study of the molecular recognition process. Among them, peanut lectin (PNA) is highly relevant in the glycobiology field, because of its specificity for β-galactosides, showing high affinity towards the Thomsen-Friedenreich (TF) antigen, a well-known tumor-associated carbohydrate antigen. Given this specificity, PNA is one of the most frequently used molecular probes for the recognition of tumor cell-surface O-glycans. Thus, it has been extensively used in glycobiology for inhibition studies with a variety of β-galactoside and β-lactoside ligands. Herein, crystal structures of PNA are reported in complex with six novel synthetic hydrolytically stable β-N- and β-S-galactosides. These complexes, along with computational simulations, disclosed key molecular binding interactions of the different sugars to PNA at the atomic level, revealing the role of specific water molecules in the protein–ligand recognition. Furthermore, binding affinity studies measured by isothermal titration calorimetry showed dissociation constant values in the micromolar range, as well as a positive glycoside cluster effect in terms of affinity in the case of the divalent compounds. Taken together, this work provides qualitative structural rationale for the upcoming synthesis of optimized glycoclusters, designed for the study of lectin-mediated biological processes. The understanding of the recognition of β-N- and β-S-galactosides with PNA represents a benchmark in protein-carbohydrate interactions since they are novel synthetic ligands not belonging to the family of O-linked glycosides.

A Review of Phytochemical and Pharmacological Studies of Inula Species

2020 ◽  
Vol 16 (5) ◽  
pp. 557-567
Author(s):  
Aparoop Das ◽  
Anshul Shakya ◽  
Surajit Kumar Ghosh ◽  
Udaya P. Singh ◽  
Hans R. Bhat
Keyword(s):  
Bacterial Infections ◽  
Chemical Constituents ◽  
Valuable Insight ◽  
Important Ingredient ◽  
Pharmacological Activities ◽  
Medicinal Uses ◽  
The Family ◽  
Pharmacological Studies ◽  
Perennial Herbs ◽  
Insight Into

Background: Plants of the genus Inula are perennial herbs of the family Asteraceae. This genus includes more than 100 species, widely distributed throughout Europe, Africa and Asia including India. Many of them are indicated in traditional medicine, e.g., in Ayurveda. This review explores chemical constituents, medicinal uses and pharmacological actions of Inula species. Methods: Major databases and research and review articles retrieved through Scopus, Web of Science, and Medline were consulted to obtain information on the pharmacological activities of the genus Inula published from 1994 to 2017. Results: Inula species are used either alone or as an important ingredient of various formulations to cure dysfunctions of the cardiovascular system, respiratory system, urinary system, central nervous system and digestive system, and for the treatment of asthma, diabetes, cancers, skin disorders, hepatic disease, fungal and bacterial infections. A range of phytochemicals including alkaloids, essential and volatile oils, flavonoids, terpenes, and lactones has been isolated from herbs of the genus Inula, which might possibly explain traditional uses of these plants. Conclusion: The present review is focused on chemical constituents, medicinal uses and pharmacological actions of Inula species and provides valuable insight into its medicinal potential.

scholarly journals Crystal Chemical Relations in the Shchurovskyite Family: Synthesis and Crystal Structures of K2Cu[Cu3O]2(PO4)4 and K2.35Cu0.825[Cu3O]2(PO4)4

Crystals ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 807
Author(s):  
Ilya V. Kornyakov ◽  
Sergey V. Krivovichev
Keyword(s):  
Crystal Structure ◽  
Crystal Structures ◽  
Structural Complexity ◽  
Crystal Chemical ◽  
X Ray Diffraction ◽  
Complexity Measures ◽  
X Ray ◽  
The Family ◽  
Similarities And Differences ◽  
Related Compounds

Single crystals of two novel shchurovskyite-related compounds, K2Cu[Cu3O]2(PO4)4 (1) and K2.35Cu0.825[Cu3O]2(PO4)4 (2), were synthesized by crystallization from gaseous phase and structurally characterized using single-crystal X-ray diffraction analysis. The crystal structures of both compounds are based upon similar Cu-based layers, formed by rods of the [O2Cu6] dimers of oxocentered (OCu4) tetrahedra. The topologies of the layers show both similarities and differences from the shchurovskyite-type layers. The layers are connected in different fashions via additional Cu atoms located in the interlayer, in contrast to shchurovskyite, where the layers are linked by Ca2+ cations. The structures of the shchurovskyite family are characterized using information-based structural complexity measures, which demonstrate that the crystal structure of 1 is the simplest one, whereas that of 2 is the most complex in the family.

An insight to the toxic effect of Sulfamerazine on Porcine Pancreatic Amylase and Lactate Dehydrogenase Activity: An in vitro study

2021 ◽  
Vol 15 ◽  
Author(s):  
Avirup Malla ◽  
Koel Mukherjee ◽  
Mukulika Mandal ◽  
Aishwarya Mukherjee ◽  
Runa Sur ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Lactic Acidosis ◽  
Conformational Changes ◽  
Bacterial Infections ◽  
Titration Calorimetry ◽  
Dependent Manner ◽  
Pancreatic Amylase ◽  
Lactate Dehydrogenase Activity ◽  
Tract Infections

Background: Sulfamerazine, a sulfonamide has been routinely used to treat various bacterial infections namely Pneumonia, Urinary tract infections, Shigellosis, Bronchitis, Prostatitis, and many more. It interferes with the bacterial folic acid biosynthesis albeit higher eukaryotes are not susceptible to its action due to the inherent absence of this specific pathway. Objective: In spite of its constant use, Sulfamerazine administration evokes serious issues like development of antibacterial resistance through environmental contamination although how it affects eukaryotic system, specifically its target identification has not been addressed in detail. Methods: Hela Cells are cultured as per standard method, amylase and lactate dehydrogenase assay are conducted using standard procedure with spectrophotometer. Binding thermodynamics and conformational study has been estimated with isothermal titration calorimetry as well as with docking. Results: Experimental observations reveal that Sulfamerazine inhibits porcine pancreatic amylase in a noncompetitive mode (IC50 of 0.96 mM). Binding of the drug to porcine pancreatic amylase is entropy driven with conformational changes of the protein as indicated by concomitant red shift. It enhances the inhibitory effects of acarbose and cetapin on their in vitro pancreatic amylase activity. It augments lipid peroxidation and promotes lactic acidosis in a dose dependent manner. Docking studies ensure effective interactions between Sulfamerazine and proteins like lactic dehydrogenase and porcine pancreatic amylase. Conclusion: Detailed study is to be conducted to confirm whether molecular scaffold of Sulfamerazine might serve as an effective repurposed drug acting as a lead molecule for the design of antidiabetic drug of future use. Alternatively, it should be prescribed with caution under specific medical situations like diabetes, cancer, hepatic disorders manifesting lactic acidosis to avoid crisis.

scholarly journals Crystal Structures of Klebsiella pneumoniae Dihydrofolate Reductase Bound to Propargyl-Linked Antifolates Reveal Features for Potency and Selectivity

2014 ◽  
Vol 58 (12) ◽  
pp. 7484-7491 ◽  
Author(s):  
Kristen M. Lamb ◽  
Michael N. Lombardo ◽  
Jeremy Alverson ◽  
Nigel D. Priestley ◽  
Dennis L. Wright ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Crystal Structures ◽  
Dihydrofolate Reductase ◽  
Next Generation ◽  
Gram Negative ◽  
Content Type ◽  
Resistant Species ◽  
Loop Conformations ◽  
The Family ◽  
Dihydrofolate Reductases

ABSTRACTResistance to the antibacterial antifolate trimethoprim (TMP) is increasing in members of the familyEnterobacteriaceae, driving the design of next-generation antifolates effective against these Gram-negative pathogens. The propargyl-linked antifolates are potent inhibitors of dihydrofolate reductases (DHFR) from several TMP-sensitive and -resistant species, includingKlebsiella pneumoniae. Recently, we have determined that these antifolates inhibit the growth of strains ofK. pneumoniae, some with MIC values of 1 μg/ml. In order to further the design of potent and selective antifolates against members of theEnterobacteriaceae, we determined the first crystal structures ofK. pneumoniaeDHFR bound to two of the propargyl-linked antifolates. These structures highlight that interactions with Leu 28, Ile 50, Ile 94, and Leu 54 are necessary for potency; comparison with structures of human DHFR bound to the same inhibitors reveal differences in residues (N64E, P61G, F31L, and V115I) and loop conformations (residues 49 to 53) that may be exploited for selectivity.

scholarly journals Structural Basis of Ubiquitin Recognition by the Ubiquitin-associated (UBA) Domain of the Ubiquitin Ligase EDD

2007 ◽  
Vol 282 (49) ◽  
pp. 35787-35795 ◽  
Author(s):  
Guennadi Kozlov ◽  
Long Nguyen ◽  
Tong Lin ◽  
Gregory De Crescenzo ◽  
Morag Park ◽  
...  
Keyword(s):  
Ubiquitin Ligase ◽  
Site Directed Mutagenesis ◽  
Structural Basis ◽  
Titration Calorimetry ◽  
Polyubiquitin Chains ◽  
C Terminus ◽  
Damage Repair ◽  
The Family ◽  
Uba Domain ◽  
Ordered Water

EDD (or HYD) is an E3 ubiquitin ligase in the family of HECT (homologous to E6-AP C terminus) ligases. EDD contains an N-terminal ubiquitin-associated (UBA) domain, which is present in a variety of proteins involved in ubiquitin-mediated processes. Here, we use isothermal titration calorimetry (ITC), NMR titrations, and pull-down assays to show that the EDD UBA domain binds ubiquitin. The 1.85Å crystal structure of the complex with ubiquitin reveals the structural basis of ubiquitin recognition by UBA helices α1 and α3. The structure shows a larger number of intermolecular hydrogen bonds than observed in previous UBA/ubiquitin complexes. Two of these involve ordered water molecules. The functional importance of residues at the UBA/ubiquitin interface was confirmed using site-directed mutagenesis. Surface plasmon resonance (SPR) measurements show that the EDD UBA domain does not have a strong preference for polyubiquitin chains over monoubiquitin. This suggests that EDD binds to monoubiquitinated proteins, which is consistent with its involvement in DNA damage repair pathways.

Synthesis, crystal structures, antimicrobial properties and enzyme inhibition studies of zinc(II) complexes of thiones

2011 ◽  
Vol 376 (1) ◽  
pp. 207-211 ◽  
Author(s):  
Muhammad Riaz Malik ◽  
Vera Vasylyeva ◽  
Klaus Merz ◽  
Nils Metzler-Nolte ◽  
Muhammad Saleem ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Enzyme Inhibition ◽  
Antimicrobial Properties ◽  
Inhibition Studies
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