RESUMO
The finding that oxygenase-catalyzed protein hydroxylation regulates animal transcription raises questions as to whether the translation machinery and prokaryotic proteins are analogously modified. Escherichia coli ycfD is a growth-regulating 2-oxoglutarate oxygenase catalyzing arginyl hydroxylation of the ribosomal protein Rpl16. Human ycfD homologs, Myc-induced nuclear antigen (MINA53) and NO66, are also linked to growth and catalyze histidyl hydroxylation of Rpl27a and Rpl8, respectively. This work reveals new therapeutic possibilities via oxygenase inhibition and by targeting modified over unmodified ribosomes.
Assuntos
Proteínas de Escherichia coli/metabolismo , Oxigenases de Função Mista/metabolismo , Oxigenases/metabolismo , Células Procarióticas/metabolismo , Ribossomos/metabolismo , Animais , Arginina/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Dioxigenases , Inibidores Enzimáticos/farmacologia , Escherichia coli/metabolismo , Proteínas de Escherichia coli/antagonistas & inibidores , Histidina/metabolismo , Histona Desmetilases , Humanos , Hidroxilação , Espectroscopia de Ressonância Magnética , Oxigenases de Função Mista/antagonistas & inibidores , Proteínas Nucleares/metabolismo , Oxigenases/antagonistas & inibidores , Proteínas Ribossômicas/metabolismoRESUMO
Mononuclear non-heme ferrous iron dependent oxygenases and oxidases constitute an extended enzyme family that catalyze a wide range of oxidation reactions. The largest known sub-group employs 2-oxoglutarate as a cosubstrate and catalysis by these and closely related enzymes is proposed to proceed via a ferryl intermediate coordinated to the active site via a conserved HXD/E...H motif. Crystallographic studies on the 2-oxoglutarate oxygenases and related enzymes have revealed a common double-stranded beta-helix core fold that supports the residues coordinating the iron. This fold is common to proteins of the cupin and the JmjC transcription factor families. The crystallographic studies on 2-oxoglutarate oxygenases and closely related enzymes are reviewed and compared with other metallo-enzymes/related proteins containing a double-stranded beta-helix fold. Proposals regarding the suitability of the active sites and folds of the 2-oxoglutarate oxygenases to catalyze reactions involving reactive oxidizing species are described.