A Designed Four-α-Helix Bundle That Binds the Volatile General Anesthetic Halothane with High Affinity

A designed cavity in the hydrophobic core of a four-alpha-helix bundle improves volatile anesthetic binding affinity.

The structural features of protein binding sites for volatile anesthetics are being explored using a defined model system consisting of a four-alpha-helix bundle scaffold with a hydrophobic core. Earlier work has demonstrated that a prototype hydrophobic core is capable of binding the volatile anesthetic halothane. Exploratory work on the design of an improved affinity anesthetic binding site i...

Four-α-Helix Bundle with Designed Anesthetic Binding Pockets I: Structural and Dynamical Analyses

Disulfide crosslinks to probe the structure and flexibility of a designed four-helix bundle protein.

The introduction of disulfide crosslinks is a generally useful method by which to identify regions of a protein that are close together in space. Here we describe the use of disulfide crosslinks to investigate the structure and flexibility of a family of designed 4-helix bundle proteins. The results of these analyses lend support to our working model of the proteins' structure and suggest that ...

The design of a four-helix bundle protein.

The design of proteins with predetermined structural properties is a necessary first step in the de novo design of novel enzymes and receptors. A major problem associated with the design of proteins is the high flexibility inherent in polypeptide chains. It has been estimated that a protein of 100 residues can adopt up to 101~176 different conformations, a number that is as large as the number ...

Redesigning the hydrophobic core of a four-helix-bundle protein.

Rationally redesigned variants of the 4-helix-bundle protein Rop are described. The novel proteins have simplified, repacked, hydrophobic cores and yet reproduce the structure and native-like physical properties of the wild-type protein. The repacked proteins have been characterized thermodynamically and their equilibrium and kinetic thermal and chemical unfolding properties are compared with t...