1UO4

Structure Based Engineering of Internal Molecular Surfaces Of Four Helix Bundles

1UO4 の概要

• エントリーDOI: 10.2210/pdb1uo4/pdb
• 関連するPDBエントリー: 1GCL 1GCM 1UNT 1UNU 1UNV 1UNW 1UNX 1UNY 1UNZ 1UO0 1UO1 1UO2 1UO3 1UO5
• 分子名称: GENERAL CONTROL PROTEIN GCN4, CHLORIDE ION, iodobenzene, ... (4 entities in total)
• 機能のキーワード: four helix bundle, cavity, iodobenzene
• 由来する生物種: SACCHAROMYCES CEREVISIAE (BAKER'S YEAST)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 8272.93

構造登録者

Yadav, M.K.,Redman, J.E.,Alvarez-Gutierrez, J.M.,Zhang, Y.,Stout, C.D.,Ghadiri, M.R. (登録日: 2003-09-15, 公開日: 2004-10-13, 最終更新日: 2024-11-13)

主引用文献

Yadav, M.K.,Redman, J.E.,Leman, L.J.,Alvarez-Gutierrez, J.M.,Zhang, Y.,Stout, C.D.,Ghadiri, M.R.
Structure-Based Engineering of Internal Cavities in Coiled-Coil Peptides
Biochemistry, 44:9723-, 2005

PubMed Abstract: Cavities and clefts are frequently important sites of interaction between natural enzymes or receptors and their corresponding substrate or ligand molecules and exemplify the types of molecular surfaces that would facilitate engineering of artificial catalysts and receptors. Even so, structural characterizations of designed cavities are rare. To address this issue, we performed a systematic study of the structural effects of single-amino acid substitutions within the hydrophobic cores of tetrameric coiled-coil peptides. Peptides containing single glycine, serine, alanine, or threonine amino acid substitutions at the buried L9, L16, L23, and I26 hydrophobic core positions of a GCN4-based sequence were synthesized and studied by solution-phase and crystallographic techniques. All peptides adopt the expected tetrameric state and contain tunnels or internal cavities ranging in size from 80 to 370 A(3). Two closely related sequences containing an L16G substitution, one of which adopts an antiparallel configuration and one of which adopts a parallel configuration, illustrate that cavities of different volumes and shapes can be engineered from identical core substitutions. Finally, we demonstrate that two of the peptides (L9G and L9A) bind the small molecule iodobenzene when present during crystallization, leaving the general peptide quaternary structure intact but altering the local peptide conformation and certain superhelical parameters. These high-resolution descriptions of varied molecular surfaces within solvent-occluded internal cavities illustrate the breadth of design space available in even closely related peptides and offer valuable models for the engineering of de novo helical proteins.

PubMed: 16008357
DOI: 10.1021/BI050742A

実験手法

X-RAY DIFFRACTION (1.7 Å)