ISBN: 978-83-60043-10-3 - eurobic9

Eurobic9, 2-6 September, 2008, Wrocław, Poland
P16. Novel Cyclic Peptides Design Modelling Structure and Reactivity of
Zn(Cys)4 Reactive Site of Protein Hsp33
E. Bourles, O. Sénèque, J. M. Latour
iRSTV/LCBM/PMB UMR 5349, CEA-Grenoble, 17 rue des martyrs, 38054 cedex 9, Grenoble, France
e-mail: emilie.bourles@cea.fr
Tetracoordinated zinc sites in metalloproteins, in which zinc is coordinated to cysteines and/or histidines, can
have multiple roles such as catalytic, structural or redox. In particular, Zn(Cys)4 sites, which are present in 3% of
proteins, were considered as structural sites since it was found that Hsp33, a molecular chaperone, as well as
Trx2, the mitochondrial thioredoxin, were regulated by the oxidation of there Zn(Cys)4 sites into disulfides
concomitant with the release of the zinc ion [1, 2, 3]. We have developed the synthesis of cyclic peptides to
reproduce the structure of Zn(Cys)4 sites in proteins, such as the structural site of PerR or the reactive site of
Hsp33. Those de novo twenty amino-acids cyclic peptides contain two CXnC motifs, one in the cycle and
another one in a linear tail grafted on the cycle, and fit quasi-perfectly the structure of the biological sites [4, 5].
Then, this new design represents an interesting approach for modelling metallic sites in protein.
Here, we present the coordination properties, the structural properties and the reactivity toward oxidation of
several peptides designed to model the Zn(Cys)4 sites of PerR and Hsp33. The behaviour of Hsp33’s closest
peptidic structural model toward complexation with metallic cations (Co 2+ , Zn 2+ ) and toward H2O2-mediated
oxidation is very closed to what is observed in the protein [6, 7].
References:
[1] Jakob U.; Muse W.; Eser, M.; Bardwell J.C.A.; Cell, 1999, 96, p.341.
[2] Won, H.S.; Low, L.Y.; Guzman, R.D.; Jakob, U.; Dyson, H.J.; J. Mol. Biol., 2004, 341(4), p.893.
[3] Collet J-F.; D’Souza J.C.; Jakob U.; Bardwell J.C.A.; J. Biol. Chem., 2003, 278(46), p.45325.
[4] Janda, I. ; Devedjiev, Y. ; Derewenda, U. ; Dauter, Z.; Bielnicki, J.; Cooper, D.R.; Graf, P.C.F.; Joachimiack
A.; Jakob, U.; Derewenda, Z.S.; Structure, 2004, 12, p.1901.
[5] Traore D.A.; El Ghazouani A.; Ilango S.; Dupuy J.; Jacquamet L.; Ferrer J.L.; Caux-Thang C.; Duarte V.;
Latour J-M.; Mol. Microbiol. 2005, 61, p.1211.
[6] Jakob U.; Eser, M.; Bardwell J.C.A.; J. Biol. Chem., 2000, 275, p.38302.
[7] Ilbert, M.; Horst, J.; Ahrens, S.; Winter, J.; Graf, P.C.F.; Lilie, H.; Jakob, U.; Nat. Struct. Mol. Biol., 2007,
14, p.556.
_____________________________________________________________________
135