1UO4

Structure Based Engineering of Internal Molecular Surfaces Of Four Helix Bundles

Summary for 1UO4

• Entry DOI: 10.2210/pdb1uo4/pdb
• Related: 1GCL 1GCM 1UNT 1UNU 1UNV 1UNW 1UNX 1UNY 1UNZ 1UO0 1UO1 1UO2 1UO3 1UO5
• Descriptor: GENERAL CONTROL PROTEIN GCN4, CHLORIDE ION, iodobenzene, ... (4 entities in total)
• Functional Keywords: four helix bundle, cavity, iodobenzene
• Biological source: SACCHAROMYCES CEREVISIAE (BAKER'S YEAST)
• Total number of polymer chains: 2
• Total formula weight: 8272.93

Authors

Yadav, M.K.,Redman, J.E.,Alvarez-Gutierrez, J.M.,Zhang, Y.,Stout, C.D.,Ghadiri, M.R. (deposition date: 2003-09-15, release date: 2004-10-13, Last modification date: 2024-05-08)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.7 Å)