RESUMO
Lectins that bind to HIV envelope glycoprotein can inhibit virus-cell fusion and be used for rational drug design. This paper presents the results of an in silico approach to improve affinity interaction between the cyanobacterial lectin microvirin and its ligand Manα(1-2)Man. Comparative modeling and molecular dynamics tools were used. Additionally, the alanine scanning webserver was used to study the importance of protein residues in the binding site and to guide mutant production. The model obtained presented two homologous domains designated as domains A and B, each consisting of a single strand with triple and antiparallel ß-sheets of (ß1-ß3 and ß6-ß8). Disulfide bonds between the cysteines (Cys60-Cys80, Cys63-Cys78 and Cys8-Cys24) were also found. The highly conserved binding site, including residues Asn44, Ile45, Asp46, Gln54, Asn55, Glu58, Thr59, Gln81, Thr82 and Met83. The RMSD values of the di-mannose and the interaction site were very stable during the molecular dynamics. Calculations of the occupation time of the hydrogen bonds were made for the residues that showed interaction in the complex lectin and ligand. The residue that contributed most to the interaction with Manα(1-2)Man was Asn55. After validation, the model generated remained stable during the entire simulation. Despite its structural similarity with the template we used, our mutant (Thr82Arg) showed a higher affinity interaction with Manα(1-2)Man. Communicated by Ramaswamy H. Sarma.
Assuntos
Lectinas , Manose , Sítios de Ligação , Humanos , Lectinas/química , Ligantes , Manose/química , Simulação de Dinâmica MolecularRESUMO
The envelope (E) protein is an important target for antibodies in flavivirus. Literature reports that the mutation T198F, located at the domain I-II hinge of the E protein, regulates viral breathing and increases the accessibility of a distal cryptic epitope located on the fusion loop, having a direct impact in the neutralization of West Nile virus (WNV). Our study aimed to describe, using accelerated molecular dynamics simulations, the effects of the T198F mutation in the flexibility of the E protein of WNV and to elucidate the mechanism that regulates epitope accessibility. The simulation results revealed that the mutation favors the formation of alternative hydrogen bonds, hampering the bending movement between domains I and II. We hypothesized that this is the mechanism by which the T198F mutation, located at the middle of the protein, locks the distal cryptc epitope near a single preferred conformation, rendering it more prone to recognition by antibodies.
Assuntos
Simulação de Dinâmica Molecular , Proteínas do Envelope Viral/metabolismo , Vírus do Nilo Ocidental/metabolismo , Anticorpos Antivirais/imunologia , Epitopos/química , Epitopos/imunologia , Ligação de Hidrogênio , Mutação/genética , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/genética , Vírus do Nilo Ocidental/genéticaRESUMO
O objetivo deste trabalho é relatar um caso de um Golden Retriever que apresentou epistaxe unilateral devido ao desenvolvimento de hemangiossarcoma na cavidade nasal direita. O paciente foi submetido ao procedimento de trepanação nasal como tratamento, não houve complicações no período pós-operatório imediato. No entanto, 90 dias após o procedimento ocorreu recidiva da neoplasia. Diversas doenças podem acometer a região nasal dos cães. As neoplasias, embora raras, são em sua maioria de origem epitelial como carcinomas, condrossarcomas, osteossarcomas, fibrossarcomas, e uma pequena porcentagem, o hemangiossarcoma. O prognóstico pode variar entre reservado à ruim, em virtude da sua alta capacidade metastática e invasão tecidual.(AU)
The objective of this study is to report a case of a Golden Retriever that presented unilateral epistaxis in consequence of hemangiosarcoma in the right nasal cavity. The patient was submitted to a nasal trepanation as treatment and presented a satisfactory result in the immediate postoperative. However, 90 days after the procedure, it was observed tumor recurrence. Various diseases can affect the nasal region of dogs. Although neoplasms are rare, the most common lesions in this region are those of epithelial origin such as carcinomas, chondrosarcomas, osteosarcomas, fibrosarcomas, and in a small percentage hemangiosarcoma. The prognosis may vary from poor to fair due its high metastatic capacity and tissue invasion.(AU)
El objetivo de este trabajo es relatar un caso de un Golden Retriever que present epistaxe unilateral debido al desarrollo de hemangiosarcoma en la cavidad nasal derecha. El paciente fue sometido al procedimiento de trepanación nasal como tratamiento, ho hubo complicaciones en el período postoperatorio inmediato. Sin embargo, 90 días después del procedimiento se produjo recidiva de la neoplasia. Dinersas enfermedade pueden acometer la region nasal de los perros. Las neoplasias, aunque raras. Son en su mayoría de origen epithelial como carcinomas, condrosarcomas, osteosarcomas, fibrosarcomas, y un pequeno porcentaje, el hemangiosarcoma. El pronóstico puede variar entre reservado a malo, debido a su alta capacidad metastática e invasion del tejido.(AU)
Assuntos
Animais , Cães , Hemangiossarcoma/veterinária , Neoplasias Nasais/cirurgia , Cavidade Nasal/patologia , Trepanação/veterinária , Recidiva Local de Neoplasia/veterináriaRESUMO
O objetivo deste trabalho é relatar um caso de um Golden Retriever que apresentou epistaxe unilateral devido ao desenvolvimento de hemangiossarcoma na cavidade nasal direita. O paciente foi submetido ao procedimento de trepanação nasal como tratamento, não houve complicações no período pós-operatório imediato. No entanto, 90 dias após o procedimento ocorreu recidiva da neoplasia. Diversas doenças podem acometer a região nasal dos cães. As neoplasias, embora raras, são em sua maioria de origem epitelial como carcinomas, condrossarcomas, osteossarcomas, fibrossarcomas, e uma pequena porcentagem, o hemangiossarcoma. O prognóstico pode variar entre reservado à ruim, em virtude da sua alta capacidade metastática e invasão tecidual.
The objective of this study is to report a case of a Golden Retriever that presented unilateral epistaxis in consequence of hemangiosarcoma in the right nasal cavity. The patient was submitted to a nasal trepanation as treatment and presented a satisfactory result in the immediate postoperative. However, 90 days after the procedure, it was observed tumor recurrence. Various diseases can affect the nasal region of dogs. Although neoplasms are rare, the most common lesions in this region are those of epithelial origin such as carcinomas, chondrosarcomas, osteosarcomas, fibrosarcomas, and in a small percentage hemangiosarcoma. The prognosis may vary from poor to fair due its high metastatic capacity and tissue invasion.
El objetivo de este trabajo es relatar un caso de un Golden Retriever que present epistaxe unilateral debido al desarrollo de hemangiosarcoma en la cavidad nasal derecha. El paciente fue sometido al procedimiento de trepanación nasal como tratamiento, ho hubo complicaciones en el período postoperatorio inmediato. Sin embargo, 90 días después del procedimiento se produjo recidiva de la neoplasia. Dinersas enfermedade pueden acometer la region nasal de los perros. Las neoplasias, aunque raras. Son en su mayoría de origen epithelial como carcinomas, condrosarcomas, osteosarcomas, fibrosarcomas, y un pequeno porcentaje, el hemangiosarcoma. El pronóstico puede variar entre reservado a malo, debido a su alta capacidad metastática e invasion del tejido.