Research Project
Grant-in-Aid for Challenging Exploratory Research
We characterized the steady-state kinetics of Trypanosoma brucei (T. brucei) GMP reductase (TbGMPR). TbGMPR but no enzymes of the host mammals was inhibited in the presence of a purine nucleotide analog ribavirin 5’-monophosphate (RMP) with a Ki value of 4.46 μM. RMP and its precursor ribavirin showed anti-parasitic effect on bloodstream forms of T. brucei in culture, and the IC50 of each compound was ranged around 25 μM. We further prepared a mutant enzyme (TbGMPR-d) lacking cystathionine β-synthase domain, which is absent in mammalian GMPRs, to determine its structure by X-ray crystallography. The structure of TbGMPR-d was resolved at 2.36Å and found to have a TIM barrel structure commonly observed in GMPRs of other organisms. However, in quaternary structure, TbGMPR-d showed a different subunit orientation as compared to that of human GMPR2. The enzyme assay revealed that the activity of TbGMPR-d was apparently lowered than the wild-type enzyme.
All 2016 2015 2014 2013 Other
All Int'l Joint Research (1 results) Journal Article (13 results) (of which Int'l Joint Research: 2 results, Peer Reviewed: 13 results, Acknowledgement Compliant: 4 results, Open Access: 5 results) Presentation (65 results) (of which Int'l Joint Research: 2 results, Invited: 10 results) Remarks (2 results)
J. Pharm. Sci.
Volume: 掲載確定 Issue: 9 Pages: 1-8
10.1016/s0022-3549(15)00176-8
PLoS Negl. Trop. Dis
Volume: 10 Issue: 1 Pages: e0004339-e0004339
10.1371/journal.pntd.0004339
Nitric Oxide
Volume: 53 Pages: 13-21
10.1016/j.niox.2015.12.005
Eur. J. Pharm. Sci.
Volume: 74 Pages: 77-85
10.1016/j.ejps.2015.04.012
J. Biol. Chem.
Volume: VOL. 290 Issue: 23 Pages: 14493-14503
10.1074/jbc.m114.635607
PLoS ONE
Volume: 10(11) Issue: 11 Pages: e0142206-e0142206
10.1371/journal.pone.0142206
Volume: 290 Issue: 43 Pages: 26072-26087
10.1074/jbc.m115.669291
Journal of Food Protection
Volume: 77 Issue: 5 Pages: 814-819
10.4315/0362-028x.jfp-13-351
J. Mol. Signal.
Volume: 9 Pages: 5-5
10.1186/1750-2187-9-5
J. Cereb. Blood. Flow. Metab
Volume: 34 Issue: 9 Pages: 1558-1567
10.1038/jcbfm.2014.127
FEBS Lett
Volume: 588 Issue: 6 Pages: 962-969
10.1016/j.febslet.2014.02.001
Parasitology
Volume: 140 Issue: 6 Pages: 735-745
10.1017/s0031182012002090
化学と生物
Volume: 51 Pages: 234-240
10031164809
http://www.bioinfo.osakafu-u.ac.jp/~inuit/