RESUMEN
The high-resolution three-dimensional structure of the plant toxin viscotoxin A3, from Viscum album L., has been determined in solution by (1)H NMR spectroscopy at pH 3.6 and 12 degrees C (the structure has been deposited in the Protein Data Bank under the id. code 1ED0). Experimentally derived restraints including 734 interproton distances from nuclear Overhauser effect measurements, 22 hydrogen bonds, 32 φ angle restraints from J coupling measurements, together with three disulphide bridge constraints were used as input in restrained molecular dynamics, followed by minimization, using DYANA and Discover. Backbone and heavy atom root-mean-square deviations were 0.47+/-0.11 A (1 A=10(-10) m) and 0.85+/-0.13 A respectively. Viscotoxin A3 consists of two alpha-helices connected by a turn and a short stretch of antiparallel beta-sheet. This fold is similar to that found in other thionins, such as crambin, hordothionin-alpha and -beta, phoratoxin A and purothionin-alpha and -beta. The difference in the observed biological activity for thionins of known structure is discussed in terms of the differences in the calculated surface potential distribution, playing an important role in their function through disruption of cell membranes. In addition, the possible role in DNA binding of the helix-turn-helix motif of viscotoxin A3 is discussed.
Asunto(s)
Muérdago/química , Preparaciones de Plantas , Proteínas de Plantas , Plantas Medicinales , Toxinas Biológicas/química , Secuencia de Aminoácidos , Membrana Celular/metabolismo , ADN/metabolismo , Concentración de Iones de Hidrógeno , Espectroscopía de Resonancia Magnética , Modelos Químicos , Modelos Moleculares , Datos de Secuencia Molecular , Unión Proteica , Estructura Secundaria de Proteína , Proteínas Inactivadoras de Ribosomas Tipo 2 , Homología de Secuencia de Aminoácido , TemperaturaRESUMEN
The viscotoxin composition of the vegetative part of V. album determined by HPLC was found to be different in the three European subspecies. The characteristic differences in viscotoxin composition were not affected by the host species and by the harvesting seasons investigated. However, host-dependent differences in the total amount of viscotoxins were detected.
RESUMEN
The complete primary structure of a cytotoxic 5 kDa polypeptide, viscotoxin A1, isolated from Viscum album L., has been determined by combining classical Edman degradation methodology with advanced mass spectrometric procedures. The same integrated approach allowed correction of the sequence of viscotoxin A2 and definition of the pattern of the disulfide bridges. The arrangement of the cysteine pairing was determined as Cys3-Cys40, Cys4-Cys32 and Cys16-Cys26. The primary structure of viscotoxin A1 shares a high degree of similarity with the known viscotoxins and more generally with the plant alpha- and beta-thionins. The pattern of S-S bridges determined for viscotoxin A2 and A1 is similar to that inferred by X-ray and NMR analysis in crambin and related to that present in alpha-purothionin and beta-hordothionin, thus indicating a highly conserved organization of the S-S pairings within the entire family. This arrangement of S-S bridges describes a peculiar structural motif, indicated as 'concentric motif', which is suggested to stabilize a common structure occurring in various small proteins able to interact with cell membranes. The distribution of the new variant toxin in different mistletoe subspecies was investigated. Viscotoxin A1 is abundant in the seeds of the three European subspecies of V. album whereas it represents a minor component in the shoots.
Asunto(s)
Cistina/análisis , Disulfuros/análisis , Disulfuros/química , Muérdago/química , Preparaciones de Plantas , Proteínas de Plantas/química , Plantas Medicinales , Toxinas Biológicas/química , Secuencia de Aminoácidos , Animales , Péptidos Catiónicos Antimicrobianos , Espectrometría de Masas , Muérdago/genética , Datos de Secuencia Molecular , Proteínas de Plantas/genética , Proteínas de Plantas/aislamiento & purificación , Proteínas Inactivadoras de Ribosomas Tipo 2 , Toxinas Biológicas/genética , Toxinas Biológicas/aislamiento & purificación , Células Tumorales Cultivadas/efectos de los fármacosRESUMEN
The polysaccharide fraction from the mucilage of Dicerocaryum zanguebaricum (Pedaliaceae) appears to be mainly constituted of a chemically homogeneous polysaccharide. By NMR and chemical degradative methods its structure appeared to consist of alternate-->4)-beta-D-GlcpA-(1--> and -->2)-alpha-D-Man p-(1-->units. Single branch units of beta-D-Xyl p and alpha-D-Gal p are linked to the O-3 positions of Man p and a significant number of Glc pA residues.
Asunto(s)
Hojas de la Planta/química , Plantas Medicinales/química , Polisacáridos/química , África , Conformación de Carbohidratos , Secuencia de Carbohidratos , Galactosa/análisis , Glucuronatos , Ácido Glucurónico , Hidrólisis , Espectroscopía de Resonancia Magnética , Manosa/análisis , Metilación , Datos de Secuencia Molecular , Oligosacáridos/química , Polisacáridos/aislamiento & purificación , Ácido Trifluoroacético/farmacología , Xilosa/análisis , alfa-Galactosidasa/metabolismoRESUMEN
We have considered just some of the many factors which may affect myocardial function, assessed by means of echocardiography, in uremic patients. Our findings support the view of a multifactorial genesis of the cardiac involvement in uremic patients.
Asunto(s)
Cardiomiopatía Hipertrófica/etiología , Uremia/complicaciones , Adulto , Anciano , Calcio/metabolismo , Cardiomiopatía Hipertrófica/metabolismo , Cardiomiopatía Hipertrófica/fisiopatología , Carnitina/sangre , Ecocardiografía , Femenino , Humanos , Hierro/metabolismo , Metabolismo de los Lípidos , Masculino , Persona de Mediana Edad , Hormona Paratiroidea/fisiología , Fósforo/metabolismo , Uremia/metabolismo , Uremia/fisiopatología , Vitamina D/fisiologíaAsunto(s)
Hipertensión Renal/tratamiento farmacológico , Fallo Renal Crónico/complicaciones , Nifedipino/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Creatinina/sangre , Femenino , Humanos , Hipertensión Renal/etiología , Fallo Renal Crónico/sangre , Masculino , Persona de Mediana Edad , Estudios RetrospectivosAsunto(s)
Hipertensión Renal/tratamiento farmacológico , Fallo Renal Crónico/complicaciones , Nifedipino/uso terapéutico , Preeclampsia/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Urgencias Médicas , Femenino , Humanos , Masculino , Persona de Mediana Edad , EmbarazoRESUMEN
The administration of rough hydrophilic extract of Eryngium maritimum L. to intact rats inhibits carrageenin induced paw oedema, but it is inactive against cotton pellet granuloma; moreover, the extract does not reduce the weight of thymus, adrenals and spleen. These data show that the anti-inflammatory effect of E. maritimum extract is unlikely to be produced by a steroid-like compound or to be a consequence of adrenal stimulation. Further fractionation of total hydrophilic extract showed that the anti-inflammatory activity is retained by a sub-alkaline fraction.