RESUMEN
Maltoporin (LamB protein) is a malto-oligosaccharide-selective pore protein in the outer membrane of Escherichia coli. The genetic basis of binding and transport specificity was investigated through cloning, mapping and sequencing lamB genes from seven independent mutants with various changes in maltodextrin binding affinities; these mutants were unchanged in binding phage lambda. Single amino acid substitutions specifically resulting in maltodextrin affinity changes were as follows: Arg8----His in two independent mutants resulted in much reduced affinity for all ligands and a smaller pore no longer selective for maltodextrins. A Trp74----Arg substitution resulted in a lower affinity for starch, a slight increase in maltose affinity but no striking pore changes. An Arg82----Ser resulted in lowered maltodextrin affinity, but increased affinity for sucrose in both binding and pore function. A Tyr118----Phe resulted in a higher affinity for both starch and maltose, a slightly larger pore and increased transport of maltohexaose by the pores. Asp121----Gly in two independent isolates resulted in a higher affinity for large dextrins and a marginally larger pore. These results suggest that the maltodextrin-selective functions reside in the N-terminal sequence of maltoporin and are separate from the phage lambda binding domains.
Asunto(s)
Proteínas de la Membrana Bacteriana Externa/genética , Proteínas de Transporte de Monosacáridos/genética , Polisacáridos/metabolismo , Receptores Virales/genética , Secuencia de Aminoácidos , Secuencia de Bases , Sitios de Unión , Mapeo Cromosómico , Clonación Molecular , Escherichia coli/genética , Genes , Genes Bacterianos , Proteínas de Transporte de Monosacáridos/metabolismo , Mutación , Porinas , Receptores Virales/metabolismo , Relación Estructura-ActividadRESUMEN
One hundred and sixty-one female patients, over the age of 70, with breast cancer were treated by Tamoxifen alone in a pilot phase II study. 61% showed objective regression of the disease and in 27% there was complete remission. The treatment was well tolerated and the survival rate compared favourably to that following conventional methods of treatment. An accurate assessment of the method awaits a randomized clinical trial.