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PDBsum entry 6g0x
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References listed in PDB file
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Key reference
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Title
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Solvent networks tune thermodynamics of oligosaccharide complex formation in an extended protein binding site.
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Authors
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S.Kunstmann,
U.Gohlke,
N.K.Broeker,
Y.Roske,
U.Heinemann,
M.Santer,
S.Barbirz.
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Ref.
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J Am Chem Soc, 2018,
140,
10447-10455.
[DOI no: ]
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PubMed id
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Abstract
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The principles of protein-glycan binding are still not well understood on a
molecular level. Attempts to link affinity and specificity of glycan recognition
to structure suffer from the general lack of model systems for experimental
studies and the difficulty to describe the influence of solvent. We have
experimentally and computationally addressed energetic contributions of solvent
in protein-glycan complex formation in the tailspike protein (TSP) of E. coli
bacteriophage HK620. HK620TSP is a 230 kDa native trimer of right-handed,
parallel beta-helices that provide extended, rigid binding sites for bacterial
cell surface O-antigen polysaccharides. A set of high-affinity mutants bound
hexa- or pentasaccharide O-antigen fragments with very similar affinities even
though hexasaccharides introduce an additional glucose branch into an occluded
protein surface cavity. Remarkably different thermodynamic binding signatures
were found for different mutants; however, crystal structure analyses indicated
that no major oligosaccharide or protein topology changes had occurred upon
complex formation. This pointed to a solvent effect. Molecular dynamics
simulations using a mobility-based approach revealed an extended network of
solvent positions distributed over the entire oligosaccharide binding site.
However, free energy calculations showed that a small water network inside the
glucose-binding cavity had the most notable influence on the thermodynamic
signature. The energy needed to displace water from the glucose binding pocket
depended on the amino acid at the entrance, in agreement with the different
amounts of enthalpy-entropy compensation found for introducing glucose into the
pocket in the different mutants. Studies with small molecule drugs have shown
before that a few active water molecules can control protein complex formation.
HK620TSP oligosaccharide binding shows that similar fundamental principles also
apply for glycans, where a small number of water molecules can dominate the
thermodynamic signature in an extended binding site.
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Secondary reference #1
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Title
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Single amino acid exchange in bacteriophage hk620 tailspike protein results in thousand-Fold increase of its oligosaccharide affinity.
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Authors
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N.K.Broeker,
U.Gohlke,
J.J.Müller,
C.Uetrecht,
U.Heinemann,
R.Seckler,
S.Barbirz.
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Ref.
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Glycobiology, 2013,
23,
59-68.
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PubMed id
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