title: Four-helix bundle cavitein reveals middle leucine as linchpin.
abstract: A template-assembled de novo four-helix bundle is used to examine the hydrophobic effect within the bundle interior. Leu to Ala variants of the basis sequence GG-EELLKKLEELLKKG were characterized by GuHCl denaturation, NMR dispersion, and N-H/D exchange experiments. The results show that the middle leucine (L7) is imperative in maintaining bundle stability. The average leucine was found to contribute 1.8 kcal mol(-1) toward stability, whereas the middle leucines contribute 2.7 kcal mol(-1) each. Substituting alanine into the middle position (7) constitutes a striking 95% reduction of the overall cavitein stability.
authors.affiliation: Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC, Canada V6T 1Z1.
authors.forename: Jon O
authors.initials: JO
authors.lastname: Freeman
authors.forename: Diana
authors.initials: D
authors.lastname: Wallhorn
authors.forename: John C
authors.initials: JC
authors.lastname: Sherman
mesh_terms: D000577:Amides / Q000737:chemistry; D000595:Amino Acid Sequence; D002942:Circular Dichroism; D041961:Deuterium Exchange Measurement; D004988:Ethers, Cyclic / Q000737:chemistry*; D019791:Guanidine / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions; D007930:Leucine / Q000737:chemistry*; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D011489:Protein Denaturation / Q000187:drug effects; D017433:Protein Structure, Secondary; D012118:Resorcinols / Q000737:chemistry*; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
chemical_list: D000577:Amides; D004988:Ethers, Cyclic; D010455:Peptides; D012118:Resorcinols; C442939:cavitand; D014867:Water; D007930:Leucine; D019791:Guanidine