Journal article
High-resolution structural characterization of a helical α/β-peptide foldamer bound to the anti-apoptotic protein Bcl-x L
EF Lee, JD Sadowsky, BJ Smith, PE Czabotar, KJ Peterson-Kaufman, PM Colman, SH Gellman, WD Fairlie
Angewandte Chemie International Edition | WILEY-BLACKWELL | Published : 2009
Abstract
Get into the groove: The first high-resolution structure of a foldamer bound to a protein target is described (see picture; foldamer in sticks). The foldamer consists of α- and β-amino acid residues and is bound to the antiapoptotic protein Bcl-xL. The overall binding mode and key interactions observed in the foldamer/Bcl-xL complex mimic those seen in complexes of Bcl-xL with natural α-peptide ligands. Additional contacts in the foldamer/Bcl-xL complex involving β-amino acid residues appear to contribute to binding affinity. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.
Grants
Awarded by National Institute of General Medical Sciences
Funding Acknowledgements
This work was supported by NIGMS grant GM-56414 (S.H.G.). J.D.S. was supported in part by an NSF Graduate Fellowship, K.J.P.-K. was supported in part by a Chemistry-Biology Interface Training Grant from NIGMS (T32 GM008505), and E.F.L., W.D.F., and P.M.C. were supported by grants and fellowships from the Cancer Council of Victoria, the NHMRC of Australia (W.D.F., P.M.C.), Australian Cancer Research Foundation (P.M.C.), and the Leukemia and Lymphoma Society (P.M.C.). Infrastructure support from NHMRC IRIIS (361646) and the Victorian State Government OIS grant is gratefully acknowledged. Crystallization trials were performed at the Bio21 Collaborative Crystallisation Centre.