ABSTRACT
In addition to phosphorylation, selective cysteine oxidation-reduction serves as an important mechanism for posttranslational modification of protein function. This mechanism, termed redox regulation , has been implicated in a variety of cellular processes such as DNA synthesis, enzyme activation, gene expression, and cell-cycle regulation (for re view, see Refs. 1 and 2). Human thioredoxin (hTRX) has been shown to be an important redox regulator in those biological processes. hTRX can function directly by interacting with the target molecules, such as NFkB transcription factor (3,4) or indirectly via another redox protein known as Ref-1. (5,6). Using multidimensional heteronuclear NMR spectroscopy (for review, see Refs. 7 and 8), we have solved the solu tion structures of hTRX complexed with its target peptides from NFkB and Ref-1. These complexes represent kinetically stable mixed disul fide intermediates along the reaction pathway and hence provide sig nificant insights into the structural basis of hTRX-mediated redox regu lation in diverse biological processes.
