RESUMO
Glioblastoma multiforme (GBM) is the most aggressive type of glioma, displaying atypical glycosylation pattern that may modulate signaling pathways involved in tumorigenesis. Lectins are glycan binding proteins with antitumor properties. The present study was designed to evaluate the antitumor capacity of the Dioclea reflexa lectin (DrfL) on glioma cell cultures. Our results demonstrated that DrfL induced morphological changes and cytotoxic effects in glioma cell cultures of C6, U-87MG and GBM1 cell lines. The action of DrfL was dependent upon interaction with glycans, and required a carbohydrate recognition domain (CRD), and the cytotoxic effect was apparently selective for tumor cells, not altering viability and morphology of primary astrocytes. DrfL inhibited tumor cell migration, adhesion, proliferation and survival, and these effects were accompanied by activation of p38MAPK and JNK (p46/54), along with inhibition of Akt and ERK1/2. DrfL also upregulated pro-apoptotic (BNIP3 and PUMA) and autophagic proteins (Atg5 and LC3 cleavage) in GBM cells. Noteworthy, inhibition of autophagy and caspase-8 were both able to attenuate cell death in GBM cells treated with DrfL. Our results indicate that DrfL cytotoxicity against GBM involves modulation of cell pathways, including MAPKs and Akt, which are associated with autophagy and caspase-8 dependent cell death.
Assuntos
Antineoplásicos , Morte Celular Autofágica , Dioclea , Glioma , Humanos , Dioclea/química , Caspase 8/metabolismo , Caspase 8/farmacologia , Caspase 8/uso terapêutico , Lectinas/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/farmacologia , Proteínas Proto-Oncogênicas c-akt/uso terapêutico , Linhagem Celular Tumoral , Glioma/tratamento farmacológico , Glioma/metabolismo , Glioma/patologia , Movimento Celular , Autofagia , Antineoplásicos/farmacologia , Proliferação de Células , ApoptoseRESUMO
A glioblastoma (GBM) is a highly malignant primary brain tumor with a poor prognosis because of its invasiveness and high resistance to current therapies. In GBMs, abnormal glycosylation patterns are associated with malignancy, which allows for the use of lectins as tools for recognition and therapy. More specifically, lectins can interact with glycan structures found on the malignant cell surface. In this context, the present work aimed to investigate the antiglioma potential of ConGF, a lectin purified from Canavalia grandiflora seeds, against C6 cells. The treatment of C6 cells with ConGF impaired the mitochondrial transmembrane potential, reduced cell viability, and induced morphological changes. ConGF also induced massive autophagy, as evaluated by acridine orange (AO) staining and LC3AB-II expression, but without prominent propidium iodide (PI) labeling. The mechanism of action appears to involve the carbohydrate-binding capacity of ConGF, and in silico studies suggested that the lectin can interact with the glycan structures of matrix metalloproteinase 1 (MMP1), a prominent protein found in malignant cells, likely explaining the observed effects.
Assuntos
Canavalia , Fabaceae , Canavalia/química , Fabaceae/química , Lectinas/química , Metaloproteinase 1 da Matriz , Propídio , Laranja de Acridina , Lectinas de Plantas/química , Sementes/química , Carboidratos/análiseRESUMO
Lectins are a class of proteins or glycoproteins capable of recognizing and interacting with carbohydrates in a specific and reversible manner. Owing to this property, these proteins can interact with glycoconjugates present on the cell surface, making it possible to decipher the glycocode, as well as elicit biological effects, such as inflammation and vasorelaxation. Here, we report a structural and biological study of the mannose/glucose-specific lectin from Dioclea lasiophylla seeds, DlyL. The study aimed to evaluate in detail the interaction of DlyL with Xman and high-mannose N-glycans (MAN3, MAN5 and MAN9) by molecular dynamics (MD) and the resultant in vitro effect on vasorelaxation using rat aortic rings. In silico analysis of molecular docking was performed to obtain the initial coordinates of the DlyL complexes with the carbohydrates to apply as inputs in MD simulations. The MD trajectories demonstrated the stability of DlyL over time as well as different profiles of interaction with Xman and N-glycans. Furthermore, aortic rings assays demonstrated that the lectin could relax pre-contracted aortic rings with the participation of the carbohydrate recognition domain (CRD) and nitric oxide (NO) when endothelial tissue is preserved. These results confirm the ability of DlyL to interact with high-mannose N-glycans with its expanded CRD, supporting the hypothesis that DlyL vasorelaxant activity occurs primarily through its interaction with cell surface glycosylated receptors.Communicated by Ramaswamy H. Sarma.
Assuntos
Dioclea , Animais , Carboidratos/química , Dioclea/química , Dioclea/metabolismo , Lectinas , Manose/química , Simulação de Acoplamento Molecular , Lectinas de Plantas/análise , Lectinas de Plantas/química , Lectinas de Plantas/farmacologia , Polissacarídeos/farmacologia , Ratos , Sementes/química , Sementes/metabolismo , Vasodilatadores/análise , Vasodilatadores/química , Vasodilatadores/farmacologiaRESUMO
Using a rat model of peritonitis, we herein report the inflammatory effect induced by the lectin isolated from Vatairea guianensis (VGL) seeds in the context of interactions between VGL and both toll-like receptor 4 (TLR4) and tumor necrosis factor receptor 1 (TNFR1). Peritoneal macrophages were stimulated with VGL for dose-dependent gene expression and release of TNF-α. In vivo results showed that VGL (1 mg/kg; intraperitoneal) induced peritonitis in female Wistar rats. Leukocyte migration, macrophage activation, and protein leakage were measured 3 and 6 hours after induction. In vitro, peritoneal macrophages were stimulated with VGL for gene expression and TNF-α dosage (mean ± SEM (n = 6), analysis of variance, and Bonferroni's test (P < .05)). In silico, VGL structure was applied in molecular docking with representative glycans. It was found that (a) VGL increases vascular permeability and stimulates leukocyte migration, both rolling and adhesion; (b) lectin-induced neutrophil migration occurs via macrophage stimulation, both in vitro and in vivo; (c) lectin interacts with TLR4 and TNFR1; and (d) stimulates TNF-α gene expression (RT-PCR) and release from peritoneal macrophages. Thus, upon lectin-glycan binding on the cell surface, our results suggest that VGL induces an acute inflammatory response, in turn activating the release of peritoneal macrophages via TNF-α and TLR and/or TNFR receptor pathways.
Assuntos
Fabaceae/química , Glicoconjugados/metabolismo , Macrófagos Peritoneais/efeitos dos fármacos , Lectinas de Plantas/farmacologia , Animais , Movimento Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Glicoconjugados/química , Leucócitos/efeitos dos fármacos , Macrófagos Peritoneais/metabolismo , Peritonite/induzido quimicamente , Peritonite/metabolismo , Peritonite/patologia , Lectinas de Plantas/química , Lectinas de Plantas/metabolismo , Ratos Wistar , Receptores Tipo I de Fatores de Necrose Tumoral/química , Receptores Tipo I de Fatores de Necrose Tumoral/metabolismo , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Glioblastoma multiforme is the most aggressive type of glioma, with limited treatment and poor prognosis. Despite some advances over the last decade, validation of novel and selective antiglioma agents remains a challenge in clinical pharmacology. Prior studies have shown that leguminous lectins may exert various biological effects, including antitumor properties. Accordingly, this study aimed to evaluate the mechanisms underlying the antiglioma activity of ConBr, a lectin extracted from the Canavalia brasiliensis seeds. ConBr at lower concentrations inhibited C6 glioma cell migration while higher levels promoted cell death dependent upon carbohydrate recognition domain (CRD) structure. ConBr increased p38MAPK and JNK and decreased ERK1/2 and Akt phosphorylation. Moreover, ConBr inhibited mTORC1 phosphorylation associated with accumulation of autophagic markers, such as acidic vacuoles and LC3 cleavage. Inhibition of early steps of autophagy with 3-methyl-adenine (3-MA) partially protected whereas the later autophagy inhibitor Chloroquine (CQ) had no protective effect upon ConBr cytotoxicity. ConBr also augmented caspase-3 activation without affecting mitochondrial function. Noteworthy, the caspase-8 inhibitor IETF-fmk attenuated ConBr induced autophagy and C6 glioma cell death. Finally, ConBr did not show cytotoxicity against primary astrocytes, suggesting a selective antiglioma activity. In summary, our results indicate that ConBr requires functional CRD lectin domain to exert antiglioma activity, and its cytotoxicity is associated with MAPKs and Akt pathways modulation and autophagy- and caspase-8- dependent cell death.
Assuntos
Antineoplásicos/farmacologia , Caspase 8/metabolismo , Ativação Enzimática/efeitos dos fármacos , Glioma/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Lectinas de Plantas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Astrócitos/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Caspase 3/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Glioma/metabolismo , Glioma/patologia , Humanos , Camundongos , Mitocôndrias/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Simulação de Acoplamento Molecular , Polissacarídeos/metabolismo , Domínios Proteicos/fisiologia , Estrutura Quaternária de Proteína/fisiologia , Estrutura Terciária de Proteína/fisiologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , RatosRESUMO
The Tn antigen is an epitope containing N-acetyl-D-galactosamine present in the extracellular matrix of some carcinoma cells in humans, and it is often used as a biomarker. Lectins are proteins capable of binding to carbohydrates and can be used as a molecular tool to recognize antigens and to differentiate cancer cells from normal cells. In this context, the present work aimed to characterize the interaction of Vatairea guianensis seed lectin with N-acetyl-D-galactosamine and the Tn antigen by molecular dynamics and molecular mechanics/Poisson-Boltzmann solvent-accessible surface area analysis. This study revealed new interacting residues not previously identified in static analysis of the three-dimensional structures of Vatairea lectins, as well as the configuration taken by the carbohydrate recognition domain, as it interacts with each ligand. During the molecular dynamics simulations, Vatairea guianensis lectin was able to bind stably to Tn antigen, which, as seen previously for other lectins, enables its use in cancer research, diagnosis, and therapy. This work further demonstrates the efficiency of bioinformatics in lectinology.
Assuntos
Fabaceae/química , Simulação de Dinâmica Molecular , Lectinas de Plantas/química , Humanos , Neoplasias , Domínios ProteicosRESUMO
Lectins are defined as proteins or glycoproteins capable of specific and reversible binding to carbohydrates. Inside this group of proteins, the most well-studied lectins belong to the Leguminosae family, and inside this family, the Diocleinae subtribe includes the most characterized lectin Concanavalin A (ConA), as well as ConBr, the lectin from Canavalia brasiliensis, the subject of this review. Since 1979, several studies have been published in the literature regarding this lectin, from its isolation and characterization to its several biological activities. This year, 2019, will mark 40 years since researchers have begun to study ConBr and 100 years since the discovery of ConA, making 2019 a momentous year for lectinology. Owing to the abundance of studies involving ConBr, this review will focus on ConBr's purification, physicochemical properties, functional and structural analyses, biological activities and biotechnological applications. This will give researchers a broad glimpse into the potential of this lectin, as well as it characteristics, as we look ahead to its expanding applications in glycomics and biotechnology.
Assuntos
Canavalia/química , Lectinas de Plantas/isolamento & purificação , Sementes/química , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Concanavalina A/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Modelos Moleculares , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Lectinas de Plantas/farmacologia , Ligação Proteica , Conformação ProteicaRESUMO
The Arachis genus belongs to the Dalbergieae tribe, a group of plants that show promising potential novel lectins. Three lectins of the well-known Arachis hypogaea have already been purified, while lectins from related species are still unknown. Genomes of two closely related species, Arachis duranensis and Arachis ipaensis, were recently sequenced. Therefore, this study aimed to establish the three-dimensional structure of Arachis duranensis lectin (ADL) and Arachis ipaensis lectin (AIL) by homology modeling, test their activity against mannosides, and perform molecular dynamics (MD) simulations on these two proteins, both unligated and interacting with mannose or α-methyl-D-mannoside. The fold obtained for the molecular models agrees with data obtained from previous leguminous lectins, showing a conserved jelly roll motif. Docking scores indicate that these lectins have different theoretical binding energy with monosaccharides, disaccharides, and high-mannose glycans. MD simulations revealed that these proteins are α-methyl-D-mannoside-specific, having less stable interactions with mannose. This study thus serves as a guide for further research on lectins of the Arachis genus.
RESUMO
Lectins represent a class of proteins or glycoproteins capable of reversibly binding to carbohydrates. Seed lectins from the Dalbergieae tribe (Leguminosae) have structural variability, carbohydrate specificity, and biological effects, such as inflammation, vasorelaxation and cancer antigen binding. To comprehensively address these factors, the present work aimed to establish and characterize the three-dimensional structure of Centrolobium microchaete lectin (CML) by homology modeling, investigate protein-carbohydrate interactions and evaluate its inflammatory effect on mice. Molecular docking was performed to analyze interactions of the lectin with monosaccharides, disaccharides and N-glycans. Two dimannosides, methyl mannose-1,3-α-D-mannose (MDM) and mannose-1,3-α-D-mannose (M13), were used in molecular dynamics (MD) simulations to study the behavior of the carbohydrate-recognition domain (CRD) over time. Results showed an expanded domain within which hydrophobic interactions with the methyl group in the MDM molecule were established, thus revealing novel interactions for mannose-specific Dalbergieae lectins. To examine its biological activities, CML was purified in a single step by affinity chromatography on Sepharose-mannose matrix. The lectin demonstrated inflammatory response in the paw edema model and stimulated leukocyte migration to the animal peritoneal cavities, an effect elicited by CRD. For the first time, this work reports the molecular dynamics of a lectin from the Dalbergieae tribe.
Assuntos
Fabaceae/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Estrutura Molecular , Lectinas de Plantas/química , Sementes/química , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Anti-Inflamatórios não Esteroides/farmacologia , Sítios de Ligação , Modelos Animais de Doenças , Edema/tratamento farmacológico , Edema/etiologia , Edema/patologia , Metais/química , Camundongos , Lectinas de Plantas/isolamento & purificação , Lectinas de Plantas/farmacologia , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Relação Estrutura-AtividadeAssuntos
Dioclea/química , Lectinas de Ligação a Manose/química , Lectinas de Plantas/química , Sementes/química , Animais , Apoptose/efeitos dos fármacos , Sítios de Ligação , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cristalização , Glioma , Lectinas de Ligação a Manose/isolamento & purificação , Lectinas de Ligação a Manose/farmacologia , Simulação de Acoplamento Molecular , Lectinas de Plantas/isolamento & purificação , Lectinas de Plantas/farmacologia , Ligação Proteica , Conformação Proteica , RatosRESUMO
Lectins are multidomain proteins that specifically recognize various carbohydrates. The structural characterization of these molecules is crucial in understanding their function and activity in systems and organisms. Most cancer cells exhibit changes in glycosylation patterns, and lectins may be able to recognize these changes. In this work, Dioclea lasiocarpa seed lectin (DLL) was structurally characterized. The lectin presented a high degree of similarity with other lectins isolated from legumes, presenting a jelly roll motif and a metal-binding site stabilizing the carbohydrate-recognition domain. DLL demonstrated differential interactions with carbohydrates, depending on type of glycosidic linkage present in ligands. As observed by the reduction of cell viability in C6 cells, DLL showed strong antiglioma activity by mechanisms involving activation of caspase 3.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Dioclea/química , Glioma/patologia , Lectinas de Plantas/química , Lectinas de Plantas/farmacologia , Animais , Antineoplásicos/metabolismo , Metabolismo dos Carboidratos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Simulação de Acoplamento Molecular , Lectinas de Plantas/metabolismo , Conformação Proteica , Ratos , Sementes/químicaRESUMO
The Pisum arvense lectin (PAL), a legume protein belonging to the Vicieae tribe, is capable of specific recognition of mannose, glucose and its derivatives without altering its structure. In this work, the three-dimensional structure of PAL was determined by X-ray crystallography and studied in detail by a combination of molecular docking and molecular dynamics (MD). Crystals belonging to monoclinic space group P21 were grown by the vapor diffusion method at 293 K. The structure was solved at 2.16 Å and was similar to that of other Vicieae lectins. The structure presented Rfactor and Rfree of 17.04% and 22.08%, respectively, with all acceptable geometric parameters. Molecular docking was performed to analyze interactions of the lectin with monosaccharides, disaccharides and high-mannose N-glycans. PAL demonstrated different affinities on carbohydrates, depending on bond orientation and glycosidic linkage present in ligands. Furthermore, the lectin interacted with representative N-glycans in a manner consistent with the biological effects described for Vicieae lectins. Carbohydrate-recognition domain (CRD) in-depth analysis was performed by MD, describing the behavior of CRD residues in complex with ligand, stability, flexibility of the protein over time, CRD volume and topology. This is a first report of its kind for a lectin of the Vicieae tribe.
Assuntos
Fabaceae/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Lectinas de Plantas/química , Polissacarídeos/química , Cristalografia por Raios XRESUMO
The lectin from Platypodium elegans seeds (PELa) was purified by affinity chromatography in a mannose-agarose column. The lectin agglutinated rabbit erythrocytes and the agglutinating effect was inhibited by previous incubation with the glycoprotein fetuin, along with N-acetyl-d-glucosamine, D-mannose and its derivatives. The lectin maintained complete activity in temperatures ranging from 40 to 60°C and pH values ranging from 9 to 10. As a glycoprotein, PELa has a carbohydrate content of 2.2%, and its activity requires divalent cations such as Ca2+ and Mn2+. Based on SDS-PAGE, PELa displays a profile similar to that of other Dalbergieae lectins with the main chain of molecular mass around 30kDa and two subunits of 19kDa and 10 kDa each. Two-dimensional (2D) electrophoresis revealed the presence of isoforms with different isoelectric points, and high-performance size exclusion chromatography (HPSEC) was performed to confirm the purity of the sample. The lectin was immobilized in CNBr-activated Sepharose 4B and successfully captured fetuin in solution, demonstrating that this lectin remains active and capable of binding carbohydrates. PELa showed effects different from those of its recombinant form in both pro- and anti-inflammatory tests.
Assuntos
Edema/induzido quimicamente , Fabaceae/química , Proteínas Imobilizadas/farmacologia , Lectinas de Plantas/farmacologia , Proteínas Recombinantes/farmacologia , Sementes/química , Sefarose/química , Animais , Eritrócitos/efeitos dos fármacos , Eritrócitos/imunologia , Hemaglutinação/efeitos dos fármacos , Proteínas Imobilizadas/química , Masculino , Lectinas de Plantas/química , Coelhos , Ratos , Proteínas Recombinantes/químicaRESUMO
Lectins are proteins, or glycoproteins, capable of reversibly binding to specific mono- or oligosaccharides via a noncatalytic domain. The Diocleinae subtribe presents lectins with high structural similarity, but different effects based on biological activity assays. This variability results from small structural differences. Therefore, in this context, the present study aimed to perform a structural analysis of the lectin from Dioclea lasiophylla Mart. ex Benth seeds (DlyL) and evaluate its inflammatory effect. To accomplish this, DlyL was purified in a single step by affinity chromatography on Sephadex® G-50 matrix. DlyL primary structure was determined through a combination of tandem mass spectrometry and DNA sequencing. DlyL showed high similarity with other species from the same genus. Its theoretical three-dimensional structure was predicted by homology modelling, and the protein was subjected to ligand screening with monosaccharides, oligosaccharides and complex N-glycans by molecular docking. Stability and binding of the lectin with α-methyl-d-mannoside were assessed by molecular dynamics. DlyL showed acute inflammatory response with hypernociceptive effect in the paw edema model, possibly by interaction with glycans present at the cell surface.
Assuntos
Lectinas/química , Simulação de Acoplamento Molecular , Dioclea/química , Simulação de Dinâmica Molecular , Monossacarídeos/química , Oligossacarídeos/química , Espectrometria de Massas em TandemRESUMO
The three-dimensional structure of Dioclea reflexa seed lectin (DrfL) was studied in detail by a combination of X-ray crystallography, molecular docking and molecular dynamics. DrfL was purified by affinity chromatography using Sephadex G-50 matrix. Its primary structure was obtained by mass spectrometry, and crystals belonging to orthorhombic space group P212121 were grown by the vapor diffusion method at 293K. The crystal structure was solved at 1.765Å and was very similar to that of other lectins from the same subtribe. The structure presented Rfactor and Rfree of 21.69% and 24.89%, respectively, with no residues in nonallowed regions of Ramachandran plot. Similar to other Diocleinae lectins, DrfL was capable of relaxing aortic rings via NO induction, with CRD participation, albeit with low intensity (32%). In silico analysis results demonstrated that DrfL could strongly interact with complex N-glycans, components of blood vessel glycoconjugates. Despite the high similarity among Diocleinae lectins, it was also reported that each lectin has unique CRD properties that influence carbohydrate binding, resulting in different biological effects presented by these molecules.
Assuntos
Dioclea/química , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Lectinas de Plantas/química , Lectinas de Plantas/farmacologia , Sementes/química , Sequência de Aminoácidos , Animais , Cristalografia por Raios X , Manosídeos/química , Manosídeos/metabolismo , Lectinas de Plantas/metabolismo , Polissacarídeos/química , Polissacarídeos/metabolismo , Domínios Proteicos , Ratos , Vasodilatadores/química , Vasodilatadores/metabolismo , Vasodilatadores/farmacologiaRESUMO
A lectin from Canavalia virosa, Diocleinae subtribe, was purified by affinity chromatography with Sephadex G-50 matrix and named ConV. The primary structure of ConV was obtained by mass spectrometry and crystals were obtained by the vapor diffusion method at 293K and belonged to orthorhombic space group P21221 with two molecules in its asymmetric unit. The structure obtained presented Rfactor and Rfree of 18.91% and 24.92% respectively, with no residues in nonallowed regions of Ramachandran plot. The crystal structure was solved at 2.53Å and was demonstrated to be very similar to other lectins from the same subtribe. In inflammatory tests, ConV elicited paw edema, but incubation of lectin with glucose beforehand was able to reduce the edematogenic effect, indicating the involvement of the carbohydrate recognition domain in this process. The lectin also showed toxicity to rat C6 glioma cells, disrupting the mitochondrial membrane potential (ΔYm) and decreasing cell viability, indicating an anticancer potential for ConV. In silico studies confirmed that ConV interacts strongly with carbohydrates that comprise the N-glycans of glycoproteins. This finding corroborates the hypothesis which holds that the lectin domain interacts with glycans in molecular targets and that this contributes to the effects observed in biological activities.
Assuntos
Anti-Inflamatórios/química , Antineoplásicos Fitogênicos/química , Extratos Vegetais/química , Sequência de Aminoácidos , Animais , Anti-Inflamatórios/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Sítios de Ligação , Canavalia , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Sequência Conservada , Cristalografia por Raios X , Ensaios de Seleção de Medicamentos Antitumorais , Ligação de Hidrogênio , Masculino , Manosídeos/química , Camundongos , Simulação de Acoplamento Molecular , Extratos Vegetais/farmacologia , Lectinas de Plantas/química , Ligação Proteica , Conformação Proteica em Folha beta , Estrutura Quaternária de Proteína , Ratos , Sementes/químicaRESUMO
The relation structure-activity of the Mimosoideae lectins of Parkia platycephala (PPL) and Parkia biglobosa (PBL) was analyzed in this study. PBL was solved by X-ray crystallography at a resolution of 2.1Å, and the crystal structure belonged to the C2221 space group. Structural organization and binding sites were also characterized. Specifically, PBL monomer consists of three ß-prism domains tandemly arranged with each one presenting a different carbohydrate recognition domain (CRD). PPL showed antinociceptive activity in the mouse model of acetic acid-induced writhes with maximal inhibitory effect by 74% at 1mg/mL. PPL also demonstrated anti-inflammatory effect causing inhibition of leukocyte migration induced by both direct and indirect chemoattractants. These PPL activities were compared to that of PBL described previously. Molecular docking of both PBL and PPL demonstrated some differences in carbohydrate-lectin interaction energy. Comparing structure and biological effects of the two lectins provided new data about their structure and the relation with its biological activities.