Hemin binds to human cytoplasmic arginyl-tRNA synthetase and inhibits its catalytic activity.

ABSTRACT: The free form of human cytoplasmic arginyl-tRNA synthetase (hcArgRS) is hypothesized to participate in ubiquitin-dependent protein degradation by offering arginyl-tRNA(Arg) to arginyl-tRNA transferase (ATE1). We investigated the effect of hemin on hcArgRS based on the fact that hemin regulates several critical proteins in the "N-end rule" protein degradation pathway. Extensive biochemical evidence has established that hemin could bind to both forms of hcArgRS in vitro. Based on the spectral changes of the Soret band on site-directed protein mutants, we identified Cys-115 as a specific axial ligand of hemin binding that is located in the Add1 domain. Hemin inhibited the catalytic activity of full-length and N-terminal 72-amino acid-truncated hcArgRSs by blocking amino acid activation. Kinet

SUBMITTER: Yang F 

PROVIDER: S-EPMC2998122 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature