tailieunhanh - Báo cáo Y học: Crystal structure of the catalytic domain of a human thioredoxin-like protein

Thioredoxin is a ubiquitous dithiol oxidoreductase found in many organisms and involved in numerous biochemical processes. Human thioredoxin-like protein (hTRXL) is differentially expressed at different development stages of human fetal cerebrum and belongs to an expanding family of thioredoxins. We have solved the crystal structure of the recombinant N-terminal catalytic domain (hTRXL-N) of ˚ hTRXL in its oxidized form at resolution. | Eur. J. Biochem. 269 2060-2068 2002 FEBS 2002 doi Crystal structure of the catalytic domain of a human thioredoxin-like protein Implications for substrate specificity and a novel regulation mechanism Jian Jin1 2 Xuehui Chen1. Yan Zhou2. Mark Bartlam1 Qing Guo1. Yiwei Liu1. Yixin Sun1. Yu Gao1 2 Sheng Ye1 Guangtao Li2 Zihe Rao1 Boqin Qiang2 and Jiangang Yuan2 1Laboratory of Structural Biology and the MOE Laboratory of Protein Science School of Life Science Engineering Tsinghua University Beijing China 2National Laboratory of Institute of Basic Medical Sciences Peking Union Medical College and Chinese Academy of Medical Sciences National Center of Human Genome Research Beijing China Thioredoxin is a ubiquitous dithiol oxidoreductase found in many organisms and involved in numerous biochemical processes. Human thioredoxin-like protein hTRXL is differentially expressed at different development stages of human fetal cerebrum and belongs to an expanding family of thioredoxins. We have solved the crystal structure of the recombinant N-terminal catalytic domain hTRXL-N of hTRXL in its oxidized form at resolution. Although this domain shares a similar three-dimensional structure with human thioredoxin hTRX a unique feature of hTRXL-N is the large number of positively charged residues distributed around the active site which has been implicated in substrate specificity. Furthermore the hTRXL-N crystal structure is monomeric while hTRXis dimeric in its four crystal structures reduced oxidized C73S and C32S C35S mutants reported to date. As dimerization is the key regulatory factor in hTRX the positive charge and lack of dimer formation of hTRXL-N suggest that it could interact with the acidic amino-acid rich C-terminal region thereby suggesting a novel regulation mechanism. Keywords dithiol oxidoreductase hTRXL crystal structure monomeric N-terminal. Thioredoxin a group of redox active proteins is both ubiquitously present and .