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Dr.
Bruno Canard and his team have been involved in research on viral
replicative enzymes for the past 5 years. The expertise of the group is
enzymology, and the subjects studied in the group are developed using an
integrated approach that makes use of crystallography, organic chemistry,
bio-computing, molecular and cellular biology techniques. The current work
of the group addresses the replicative enzymes of a large number of human
viral pathogens using structural genomics and functional analyses.
The AFMB laboratory has a large
expertise in X-ray crystallography, with an average of 30 new structures
solved per year, including structures solved both by NMR and by MAD/SAD
techniques. About 70 researchers and technical assistants are working in
this laboratory. The group involved in this project consists of researchers
from the Virology team of Dr. Bruno Canard.
The Virology team of
the AFMB is currently involved in a program dedicated to the cloning/expression/purification/crystallisation
of many viral proteins useful for drug design. The technology for automated
protein expression and crystallisation has been set-up and is now totally
operative. A collaborative network of virology laboratories is providing
PCR products corresponding to different viral enzymes or enzyme
sub-domains. These products are then subcloned using the Gateway technology
and proteins are expressed, purified, and crystallized through a technical
platform in work at the AFMB. The platform makes use of robots able to
streamline these processes as much as possible, from cloning to the
formerly tedious crystal growth and enzymatic characterization.
Selected
publications Partner 7:
- Campanacci V., Egloff
M.P., Longhi S., Ferron F., Rancurel C., Salomoni A., Durousseau C.,
Tocque F., Bremond N., Dobbe J.C., Snijder E.J., Canard B., and
Cambillau C. 2003. Structural genomics of the SARS coronavirus:
cloning, expression, crystallisation and preliminary crystallographic
study of the Nsp9 protein. Acta Crystallogr. D Biol. Crystallogr.
59:1628-1631
- Egloff M.P., Benarroch
D., Selisko B., Romette J.L., and Canard B. 2002 An RNA cap
(nucleoside-2'-O-) methyltransferase in the flavivirus RNA polymerase
NS5: crystal structure and functional characterisation. EMBO J.
21:2757-2768.
- Ferron F., Longhi S.,
Henrissat B., and Canard B. 2002. Viral RNA-polymerases - A predicted
2'-O-ribose methyltransferase domain shared by all
Mononegavirales. Trends Biochem. Sci., 27:222-224.
- Selmi B., Boretto J.,
Sarfati S.R., Guerreiro C., and Canard B. 2001. Mechanism-Based
Suppression of Dideoxynucleotide Resistance by K65R Human
Immunodeficiency Virus Reverse Transcriptase Using an
a-Boranophosphate Nucleoside Analogue. J. Biol. Chem. 276:48466-48472.
- Meyer P., Schneider B.,
Sarfati S., Deville-Bonne D., Guerreiro C., Boretto J., Janin J.,
Véron M., and Canard B. 2000. Structural basis for activation of
a-boranophosphate nucleotide analogues targeting drug resistant
reverse transcriptase. EMBO J. 19:3520-3529.
Dr Bruno Canard
bruno.canard@afmb.univ-mrs.fr
Dr Jean-Claude Guillemot
Jean-Claude.Guillemot@afmb.univ-mrs.fr
Claire Debarnot
claire.debarnot@afmb.univ-mrs.fr
Dr Isabelle Imbert
Isabelle.Imbert@afmb.univ-mrs.fr
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