An exposed cysteine residue of human angiostatic mini tryptophanyl-tRNA synthetase.
Human tryptophanyl-tRNA synthetase (TrpRS) catalyzes the aminoacylation of tRNA(Trp). Human TrpRS exists in two forms: a major form that is the full-length protein and a truncated form (mini TrpRS) in which most of the N-terminal extension is absent. Human mini, but not full-length, TrpRS has angiostatic activity. Because the full-length protein, which lacks angiostatic activity, has all of the amino acid determinants of the mini form, which has activity, I searched for conformational differences between the two proteins. Using a disulfide cross-linking assay, I showed that the molecular environment around Cys62 is significantly different between the two proteins. This difference can be explained by inspection of the three-dimensional structure of the full-length protein. These results give a clear demonstration of a significant difference, around a specific residue (Cys62), between a potent angiostatic and nonangiostatic version of human TrpRS.
Wakasugi
Keisuke
K
Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan. wakasugi@bio.c.u-tokyo.ac.jp
D049148:Aminoacylation; D043165:Angiostatic Proteins / Q000737:chemistry* / Q000235:genetics; D002850:Chromatography, Gel; D002942:Circular Dichroism; D003545:Cysteine / Q000737:chemistry*; D004220:Disulfides / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D006801:Humans; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation; D055503:Protein Multimerization; D012364:RNA, Transfer, Trp / Q000737:chemistry; D014369:Tryptophan-tRNA Ligase / Q000737:chemistry* / Q000235:genetics
D043165:Angiostatic Proteins; D004220:Disulfides; D012364:RNA, Transfer, Trp; D014369:Tryptophan-tRNA Ligase; D003545:Cysteine