Abstract
Protein disulfide isomerase-P5 (P5) is thought to have important functions as an oxidoreductase, however, molecular functions of P5 have not been fully elucidated. We have reported that P5 has insulin reductase activity and inhibits lysozyme refolding by formation of lysozyme multimers with hypermolecular mass inactivated by intermolecular disulfides (hyLYS) in oxidative refolding of reduced denatured lysozyme. To explore the role of each domain of P5, we investigated the effects of domain deletion and Cys-Ala mutants of P5 on insulin reduction and the oxidative refolding of the lysozyme. The mutants of catalytic cysteines, C36/39A, C171/174A, and C36/39/171/174A inhibited the lysozyme refolding almost similarly to P5, and even b domain without catalytic cysteines showed moderate inhibitory effect, suggesting that the b domain played a key role in the inhibition. Western blotting analysis of the refolding products indicated that the catalytic cysteines in both the a and a' domains cross-linked lysozyme comparably to form hyLYS resistant to trypsin, in which b domain was suggested to capture lysozyme for the significant sulfhydryl oxidation. The mutant of the conserved cysteines in b domain, C272/278A, did not form hyLYS, howeve...Continue Reading
References
Feb 1, 1995·Current Opinion in Structural Biology·R B Freedman
Jul 15, 1993·Gene·Y UedaI Kumagai
Feb 16, 2002·The EMBO Journal·Tiziana AnelliRoberto Sitia
Sep 3, 2002·Journal of Biochemistry·Masakazu KikuchiYoshiyuki Tsujimoto
Oct 9, 2002·Genes & Development·Kazuyuki HoshijimaDavid Jonah Grunwald
Aug 12, 2004·Nucleic Acids Research·Lei ZhengJean-Louis Reymond
Oct 7, 2004·Blood·Peter A JordanJonathan M Gibbins
Oct 12, 2004·The Journal of Biological Chemistry·Marcel van LithAdam M Benham
Jan 12, 2005·EMBO Reports·Lars Ellgaard, Lloyd W Ruddock
Dec 21, 2005·Journal of Molecular Biology·Emilia PedoneSimonetta Bartolucci
Jan 18, 2006·Cell·Geng TianHermann Schindelin
Aug 29, 2006·Journal of Molecular Biology·Katia D'AmbrosioSimonetta Bartolucci
Apr 11, 2007·Proceedings of the National Academy of Sciences of the United States of America·Kiranmai GumireddyQihong Huang
Sep 26, 2007·The FEBS Journal·Feras Hatahet, Lloyd W Ruddock
Jan 3, 2008·The FEBS Journal·Hiroyuki WadahamaReiko Urade
May 30, 2009·Antioxidants & Redox Signaling·Feras Hatahet, Lloyd W Ruddock
Nov 6, 2009·Journal of Cell Science·Catherine E JessopNeil J Bulleid
Feb 16, 2010·Biochimica Et Biophysica Acta·Kuniko AkamaTosifusa Toda
May 19, 2010·The FEBS Journal·Anna-Riikka Karala, Lloyd W Ruddock
Feb 1, 2011·The Plant Cell·Yayoi OndaYasushi Kawagoe
Jan 10, 2013·Plant Signaling & Behavior·Yayoi Onda, Yasushi Kawagoe
Sep 18, 2013·The Journal of Cell Biology·Kazutaka ArakiKazuhiro Nagata
Jun 12, 2014·Science Signaling·Jody GroenendykMarek Michalak