scholarly journals Biochemical Characterization of Toxoplasma gondii Mitochondrial Type II NADH Dehydrogenase Isoform I as a potential Drug Target

2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
San San Lin ◽  
Stefan Kerscher ◽  
Wolfgang Bohne
Keyword(s):  
Toxoplasma Gondii ◽  
Drug Target ◽  
Nadh Dehydrogenase ◽  
Biochemical Characterization ◽  
Potential Drug Target ◽  
Type Ii ◽  
Potential Drug

Targeting Heat Shock Proteins 60 and 70 of Toxoplasma gondii as a Potential Drug Target: In Silico Approach

2015 ◽  
Vol 8 (4) ◽  
pp. 374-387 ◽  
Author(s):  
Kaur Ashwinder ◽  
Mee Teck Kho ◽  
Phui Mun Chee ◽  
Wui Zhuan Lim ◽  
Ivan K. S. Yap ◽  
...  
Keyword(s):  
Heat Shock ◽  
Toxoplasma Gondii ◽  
Heat Shock Proteins ◽  
In Silico ◽  
Drug Target ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Shock Proteins

Toxoplasma gondii Hsp90 is a Potential Drug Target Whose Expression and Subcellular Localization are Developmentally Regulated

2005 ◽  
Vol 350 (4) ◽  
pp. 723-734 ◽  
Author(s):  
Pablo C. Echeverria ◽  
Mariana Matrajt ◽  
Omar S. Harb ◽  
María P. Zappia ◽  
Monica A. Costas ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Subcellular Localization ◽  
Drug Target ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Developmentally Regulated

scholarly journals Molecular and Kinetic Characterization of Babesia microti Gray Strain Lactate Dehydrogenase as a Potential Drug Target

2014 ◽  
Vol 8 ◽  
pp. DTI.S16504 ◽  
Author(s):  
Patrick Vudriko ◽  
Tatsunori Masatani ◽  
Shinuo Cao ◽  
Mohamad Alia Terkawi ◽  
Ketsarin Kamyingkird ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Drug Target ◽  
Babesia Microti ◽  
Potential Drug Target ◽  
Kinetic Characterization ◽  
Potential Drug

scholarly journals Type 2 NADH Dehydrogenase Is the Only Point of Entry for Electrons into theStreptococcus agalactiaeRespiratory Chain and Is a Potential Drug Target

mBio ◽  
2018 ◽  
Vol 9 (4) ◽  
Author(s):  
Andrea M. Lencina ◽  
Thierry Franza ◽  
Matthew J. Sullivan ◽  
Glen C. Ulett ◽  
Deepak S. Ipe ◽  
...  
Keyword(s):  
Respiratory Chain ◽  
Drug Target ◽  
Nadh Dehydrogenase ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Intact Cells ◽  
Content Type ◽  
Oxygen Reductase ◽  
Tract Infections

ABSTRACTThe opportunistic pathogenStreptococcus agalactiaeis the major cause of meningitis and sepsis in a newborn’s first week, as well as a considerable cause of pneumonia, urinary tract infections, and sepsis in immunocompromised adults. This pathogen respires aerobically if heme and quinone are available in the environment, and a functional respiratory chain is required for full virulence. Remarkably, it is shown here that the entire respiratory chain ofS. agalactiaeconsists of only two enzymes, a type 2 NADH dehydrogenase (NDH-2) and a cytochromebdoxygen reductase. There are no respiratory dehydrogenases other than NDH-2 to feed electrons into the respiratory chain, and there is only one respiratory oxygen reductase to reduce oxygen to water. AlthoughS. agalactiaegrows well invitroby fermentative metabolism, it is shown here that the absence of NDH-2 results in attenuated virulence, as observed by reduced colonization in heart and kidney in a mouse model of systemic infection. The lack of NDH-2 in mammalian mitochondria and its important role for virulence suggest this enzyme may be a potential drug target. For this reason, in this study,S. agalactiaeNDH-2 was purified and biochemically characterized, and the isolated enzyme was used to screen for inhibitors from libraries of FDA-approved drugs. Zafirlukast was identified to successfully inhibit both NDH-2 activity and aerobic respiration in intact cells. This compound may be useful as a laboratory tool to inhibit respiration inS. agalactiaeand, since it has few side effects, it might be considered a lead compound for therapeutics development.IMPORTANCES. agalactiaeis part of the human intestinal microbiota and is present in the vagina of ~30% of healthy women. Although a commensal, it is also the leading cause of septicemia and meningitis in neonates and immunocompromised adults. This organism can aerobically respire, but only using external sources of heme and quinone, required to have a functional electron transport chain. Although bacteria usually have a branched respiratory chain with multiple dehydrogenases and terminal oxygen reductases, here we establish thatS. agalactiaeutilizes only one type 2 NADH dehydrogenase (NDH-2) and one cytochromebdoxygen reductase to perform respiration. NADH-dependent respiration plays a critical role in the pathogen in maintaining NADH/NAD+redox balance in the cell, optimizing ATP production, and tolerating oxygen. In summary, we demonstrate the essential role of NDH-2 in respiration and its contribution toS. agalactiaevirulence and propose it as a potential drug target.

scholarly journals Identification and Characterization of a Major Cell Wall-Associated Iron-Regulated Envelope Protein (Irep-28) in Mycobacterium tuberculosis

2006 ◽  
Vol 13 (10) ◽  
pp. 1137-1142 ◽  
Author(s):  
Veena C. Yeruva ◽  
Sridevi Duggirala ◽  
V. Lakshmi ◽  
Daniel Kolarich ◽  
Friedrich Altmann ◽  
...  
Keyword(s):  
Cell Wall ◽  
Mycobacterium Tuberculosis ◽  
Envelope Protein ◽  
Drug Target ◽  
Iron Limitation ◽  
Potential Drug Target ◽  
Potential Drug ◽  
Tuberculosis Patients ◽  
Identification And Characterization

ABSTRACTIron limitation and the expression of mycobactin and carboxymycobactin byMycobacterium tuberculosisare known. Here, we report how iron regulated the coordinate expression of these two siderophores and a 28-kDa cell wall-associated iron-regulated protein (Irep-28). Irep-28 is identified as the DNA-binding HU homologue HupB protein (hupB[Rv2986c]). Antibodies to this protein were detected in sera from tuberculosis patients. The location of the protein in the cell wall makes it a potential drug target.

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