Chemical Biology and Molecular Tools for Sulfur Metabolic Compounds.
D. Padovani, Isabelle Artaud, M. Dulac (PhD 2015-2018)
Dr. V. Baland (LEM -
Université Paris 7 - Comue SPC), Dr. F. Blachier & Dr. A. Lan (AgroParisTech),
Dr. F. Bouillaud - Institut Cochin - Comue SPC), Dr. B.
Chadefaux-Vekemans), Dr. X. Norel (Hôpital Bichat - Université Paris Nord), Pr.
Dr. P. Hildebrandt (Technische Universität Berlin, Germany), Dr. B. Kloesh
(Ludwig Boltzmann Institute for Rheumatology, Balneology and Rehabilitation,
Methionine metabolism furnishes cells with important sulfur
metabolic compounds, e.g. S-adenosylmethionine (SAM), glutathione (GSH),
taurine, cysteine (Cys) and hydrogen sulfide (H2S) (Figure). H2S
is a small gaseous molecule endogeneously produced mainly by two enzymes from
the transsulfuration pathway, cystathionine beta-synthase (CBS) and
cystathionine gamma-lyase (CSE) (Figure). It emerges, along with nitric oxide NO
and carbon monoxide CO, as a new gaseous signaling molecule in mammals. H2S
exerts important functions in the cardiovascular system and the central nervous
system and is an endogenous regulator of inflammatory response. Under
physiological conditions, it exist as a mixture of the neutral hydrophobic H2S
and the charged hydrophilic HS- (pKa = 6.78 at pH 7.4 and 37°C). Added to its
small size, this grants him access to various metal ions localized in proteins
active site, and could mediate some of H2S diverse biological
effects. H2S may also signal through interaction with NO and
formation of thionitrous acid (HSNO) or nitrosopersulfide (SSNO-), appears to
modulate targeted proteins activity through persulfide formation, and is
involved in second messenger electrophilic signaling.
above-mentioned reactions involve oxidation of H2S, which like
biological thiols can act as pro-oxidant (dashed-bold arrows). Therefore, their
metabolism is strongly regulated, but the impairment of redox-based
signaling under oxidative stress conditions induces a shift in thiol/redox
signaling pathways such as thiyl radicals formation as precursors of
irreversible protein damage, glutathioniyl radicals generation, autoxidation of
H2S contributing to DNA damage,..., often associated with severe
context, in collaboration with biologists sharing our interest in H2S,
we use various techniques (biochemistry, organic and bioinorganic chemistry,
analytical methods) to :
(i) explore the
biological and bio-inorganic chemistry of sulfur compounds in the context of H2S
(ii) explore the impact of
pathological conditions on H2S biogenesis or RSH/H2S
(iii) develop analytical
and chemical tools to investigate the role of H2S in biology
►Sulfheme formation during homocysteine S-oxygenation by catalase in cancers and neurodegenerative diseases..
Padovani D., Hessani A., Castillo F. T., Liot G., Andriamihaja M., Lan A., Pilati C., Blachier F., Sen S., Galardon E. & Artaud I..
Nat. Commun. 2016, 7, 13386.
►Improved tag-switch method
reveals that thioredoxin acts as depersulfidase and controls the intracellular
levels of protein persulfidation.
Wedmann R, Onderka C, Wei S, Szijártó IA, Miljkovic JL,
Mitrovic A, Lange M, Savitsky S, Yadav PK, Torregrossa R, Harrer EG, Harrer T,
Ishii I, Gollasch M, Wood ME, Galardon E, Xian M, Whiteman M, Banerjee R,
Chem. Sci. . 2016, May 25 ;7(5):3414-3426.
►Reactivity of Persulfides Towards Strained
Bicyclo[6.1.0]nonyne Derivatives : Relevance to Chemical Tagging of Proteins.
Bioconj. Chem., 2015, 26, 1013-1016
►A Persulfide Analog of the Nitrosothiol SNAP :
Formation, Characterization and Reactivity.
I. Artaud, E.
ChemBioChem, 2014, 15(16), 2361- 4,
also see : Nat. Chem. Biol, 2014, 10,876
►Electrophilic Sulfhydration of 8-nitro-cGMP
Involves Sulfane Sulfur
V. Terzic, D. Padovani, V.
Balland, I. Artaud, E. Galardon
Org. Biomol. Chem, 2014, 12,
►New Biologically Active H2S Donors
T. Roger, F.
Raynaud , F. Bouillaud, C. Ransy, S. Simonet, C. Crespo, M.-P.
Bourguignon, N. Villeneuve, J.-P. Vilaine, I. Artaud, E. Galardon
ChemBioChem, 2013, 14,2268-2271
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