Four-alpha-helix bundle with designed anesthetic binding pockets. Part I: structural and dynamical analyses.

ABSTRACT: The four-alpha-helix bundle mimics the transmembrane domain of the Cys-loop receptor family believed to be the protein target for general anesthetics. Using high resolution NMR, we solved the structure (Protein Data Bank ID: 2I7U) of a prototypical dimeric four-alpha-helix bundle, (Aalpha(2)-L1M/L38M)(2,) with designed specific binding pockets for volatile anesthetics. Two monomers of the helix-turn-helix motif form an antiparallel dimer as originally designed, but the high-resolution structure exhibits an asymmetric quaternary arrangement of the four helices. The two helices from the N-terminus to the linker (helices 1 and 1') are associated with each other in the dimer by the side-chain ring stacking of F12 and W15 along the long hydrophobic core and by a nearly perfect stretch of hydrop

SUBMITTER: Ma D 

PROVIDER: S-EPMC2480675 | biostudies-literature | 2008 Jun

REPOSITORIES: biostudies-literature