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PDBsum entry 5b1c
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Immune system
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PDB id
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5b1c
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References listed in PDB file
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Key reference
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Title
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Modeling and experimental assessment of a buried leu-Ile mutation in dengue envelope domain III.
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Authors
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M.R.Kulkarni,
N.Numoto,
N.Ito,
Y.Kuroda.
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Ref.
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Biochem Biophys Res Commun, 2016,
471,
163-168.
[DOI no: ]
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PubMed id
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Abstract
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Envelope protein domain III (ED3) of the dengue virus is important for both
antibody binding and host cell interaction. Here, we focused on how a L387I
mutation in the protein core could take place in DEN4 ED3, but cannot be
accommodated in DEN3 ED3 without destabilizing its structure. To this end, we
modeled a DEN4_L387I structure using the Penultimate Rotamer Library and taking
the DEN4 ED3 main-chain as a fixed template. We found that three out of seven
Ile(387) conformers fit in DEN4 ED3 without introducing the severe atomic
clashes that are observed when DEN3 serotype's ED3 is used as a template. A more
extensive search using 273 side-chain rotamers of the residues surrounding
Ile(387) confirmed this prediction. In order to assess the prediction, we
determined the crystal structure of DEN4_L387I at 2 Å resolution. Ile(387)
indeed adopted one of the three predicted rotamers. Altogether, this study
demonstrates that the effects of single mutations are to a large extent
successfully predicted by systematically modeling the side-chain structures of
the mutated as well as those of its surrounding residues using fixed main-chain
structures and assessing inter-atomic steric clashes. More accurate and reliable
predictions require considering sub-angstrom main-chain deformation, which
remains a challenging task.
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