Identification of new inhibitors for alternative NADH dehydrogenase (NDH-II).
In bacterial membranes and plant, fungus and protist mitochondria, NADH dehydrogenase (NDH-II) serves as an alternative NADH : quinone reductase, a non-proton-pumping single-subunit enzyme bound to the membrane surface. Because NDH-II is absent in mammalian mitochondria, it is a promising target for new antibiotics. However, inhibitors for NDH-II are rare and unspecific. Taking advantage of the simple organization of the respiratory chain in Gluconobacter oxydans, we carried out screening of natural compounds and identified scopafungin and gramicidin S as inhibitors for G. oxydans NDH-II. Further, we examined their effects on Mycobacterium smegmatis and Plasmodium yoelii NDH-II as model pathogen enzymes.
Mogi
Tatsushi
T
Department of Biomedical Chemistry, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. tmogi@m.u-tokyo.ac.jp
Matsushita
Kazunobu
K
Murase
Yoshiro
Y
Kawahara
Kenji
K
Miyoshi
Hideto
H
Ui
Hideaki
H
Shiomi
Kazuro
K
Omura
Satoshi
S
Kita
Kiyoshi
K
D000818:Animals; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D020600:Gluconobacter oxydans / Q000201:enzymology*; D006096:Gramicidin / Q000494:pharmacology*; D007700:Kinetics; D007783:Lactones / Q000494:pharmacology; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D020102:Mycobacterium smegmatis / Q000187:drug effects / Q000201:enzymology; D009245:NADH Dehydrogenase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D010967:Plasmodium yoelii / Q000187:drug effects / Q000201:enzymology
D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D007783:Lactones; D006096:Gramicidin; D009245:NADH Dehydrogenase; C000770:scopafungin