RESUMO
In this minireview, we describe the radical S-adenosylmethionine enzymes involved in the biosynthesis of thiamin, menaquinone, molybdopterin, coenzyme F420, and heme. Our focus is on the remarkably complex organic rearrangements involved, many of which have no precedent in organic or biological chemistry.
Assuntos
Coenzimas/metabolismo , Radicais Livres/química , Proteínas Metiltransferases/metabolismo , S-Adenosilmetionina/metabolismo , Animais , Coenzimas/química , Heme/química , Heme/metabolismo , Humanos , Metaloproteínas/química , Metaloproteínas/metabolismo , Metilação , Cofatores de Molibdênio , Pteridinas/química , Pteridinas/metabolismo , S-Adenosilmetionina/química , Tiamina/química , Tiamina/metabolismo , Vitamina K 2/química , Vitamina K 2/metabolismoAssuntos
Produtos Biológicos/metabolismo , Quadruplex G , Genes myc/genética , Espectrometria de Massas por Ionização por Electrospray/métodos , Antineoplásicos/metabolismo , Antineoplásicos/farmacologia , Sequência de Bases , Produtos Biológicos/farmacologia , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Dados de Sequência Molecular , Ligação Proteica , TemperaturaRESUMO
This study has demonstrated the formation of the G-quadruplex structure from the G-rich sequence in the promoter region of the bcl-2 oncogene; the formation could be induced by addition of NH(4)(+) or K(+) ions. The binding affinity and stoichiometry of seven small molecules with the G-quadruplex were examined by using ESI-MS, as well as CD and UV spectroscopy. The binding-affinity order was determined to be P1 approximately = P5 > P2 > P3 approximately = P4 > P7 > P6. In particular, the small-molecule induction of the structural transition between the G-quadruplex and duplex DNA forms in this promoter region was investigated by ESI-MS. We directly observed specific binding of dehydrocorydaline (P7) and cationic porphyrin (P5) in one system consisting of the G-quadruplex and the duplex DNA, respectively. The results indicate that P7 selectively stabilizes the G-quadruplex and shifts the equilibrium toward G-quadruplex formation of the bcl-2 promoter, whereas P5 converts the G-quadruplex into the duplex DNA, which results in strong and selective binding to the duplex form. Therefore, P5 and P7 with their attractive binding specificities could be considered as precursors for pathway-specific drug design for regulation of bcl-2 oncogene transcription.