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PDBsum entry 1uo2
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Four helix bundle
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PDB id
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1uo2
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References listed in PDB file
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Key reference
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Title
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Structure-Based engineering of internal cavities in coiled-Coil peptides.
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Authors
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M.K.Yadav,
J.E.Redman,
L.J.Leman,
J.M.Alvarez-Gutiérrez,
Y.Zhang,
C.D.Stout,
M.R.Ghadiri.
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Ref.
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Biochemistry, 2005,
44,
9723-9732.
[DOI no: ]
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PubMed id
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Abstract
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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.
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