1UNW

Structure Based Engineering of Internal Molecular Surfaces Of Four Helix Bundles

Summary for 1UNW

• Entry DOI: 10.2210/pdb1unw/pdb
• Related: 1CE9 1DGC 1ENV 1FAV 1GCL 1GCM 1GK6 1GZL 1IHQ 1IJ0 1IJ1 1IJ2 1IJ3 1KQL 1LD4 1LLM 1NKN 1PIQ 1RB1 1RB4 1RB5 1RB6 1SWI 1TMZ 1UNT 1UNU 1UNV 1UNX 1UNY 1UNZ 1UO0 1UO1 1UO2 1UO3 1UO4 1UO5 1W5G 1W5H 1W5I 1W5J 1W5K 1W5L 1YSA 1ZII 1ZIJ 1ZIK 1ZIL 1ZIM 1ZTA 2DGC 2ZTA
• Descriptor: GENERAL CONTROL PROTEIN GCN4 (2 entities in total)
• Functional Keywords: four helix bundle, cavity
• Biological source: SACCHAROMYCES CEREVISIAE (BAKER'S YEAST)
• Cellular location: Nucleus: P03069
• Total number of polymer chains: 2
• Total formula weight: 8033.46

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: 2024-10-16)

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 (2.2 Å)