Structure
In Cristallo Screening and In Situ Ligand Bridging
alanine A162, glycines G43 and G130, and glutamate E263. In all the structures
solved, the electron density was clear for the residues G43 and A162, which
are two conserved residues buried in the active site. Their conformation is
very well defined in all the structures of LmNADK1 solved so far. Conversely,
G130 belongs to a flexible loop with a locally weak electron density due to
alternating conformation. Similarly, E263 may exist in alternating confor-
mation, although only the major one can be modeled. This glutamate is only
two residues ahead of the polyhistidine tag forming a highly mobile C-terminal
tail. Indeed, the affinity tag could not be modeled in most protein-ligand
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ACKNOWLEDGMENTS
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We thank Jean-Fran c¸ ois Guichou, Martin Cohen-Gonsaud, William Bourguet,
and Cathy Royer for helpful discussion. We acknowledge corrections of
English language in the manuscript by Lucas Black. We also acknowledge
the people at the ESRF (Grenoble, France) for the beamlines for biological
crystallography, ID14-1, ID14-2, ID14-4, and ID29. We thank Pierre Germain
and Genevi e` ve Aubert for cytotoxic assays on HeLa and MRC5 cells, respec-
tively. We acknowledge financial support from the CNRS, INSERM, Institut
Pasteur, Institut Curie, and the ANR (Blanc 06-1_137054). M.G. and L.M.
were supported by grants from the ANR.
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Received: January 6, 2012
Revised: March 9, 2012
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Kuriyan, J. (2000). Structural mechanism for STI-571 inhibition of abelson
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Accepted: March 30, 2012
Published online: May 17, 2012
1116 Structure 20, 1107–1117, June 6, 2012 ª2012 Elsevier Ltd All rights reserved