RESUMO
Redox potentials for two inactivating intrasubunit disulfides that link helix-5 and helix-9 in mutant Escherichia coli malate dehydrogenases have been determined. The Em is -285 mV when cysteines are at positions 121 and 305 and -295 mV when the cysteines are at positions 122 and 305. Oxidation to the disulfide affects kcat but not Km values. In the single V121C and N122C mutants, the Cys in helix-5 affects the Km for oxalacetate. The pH optimum in the direction of malate formation is affected by the redox state of the enzyme. Clearly, a disulfide bond can and does form between Cys residues substituted into positions 121 or 122 in the nucleotide binding domain and 305 in the carbon substrate binding domain of this NAD-dependent malate dehydrogenase. Apparently, crosslinking the domains interferes with catalysis.
Assuntos
Escherichia coli/enzimologia , Malato Desidrogenase/metabolismo , Oxirredução , Catálise , Cisteína/química , Dissulfetos , Concentração de Íons de Hidrogênio , Cinética , Malato Desidrogenase/química , Modelos Moleculares , Mutagênese , NAD/química , Oxigênio/metabolismo , Proteínas de Plantas/química , Engenharia de Proteínas , Estrutura Terciária de Proteína , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismoRESUMO
A 42 year old man with chronic renal failure and homograft transplantation developed adult T-cell lymphoma in one native kidney. The role of transfusion in the acquisition of human T-lymphotropic virus type 1 and its role in the early development of adult T cell lymphoma, particularly on the background of chronic immunosuppression, are discussed. To our knowledge, this is the first such case. (AU)
