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2016 ; 26
(7
): 772-783
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gab.com Text
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English Wikipedia
Combining 3D structure with glycan array data provides insight into the origin of
glycan specificity
#MMPMID26911287
Grant OC
; Tessier MB
; Meche L
; Mahal LK
; Foley BL
; Woods RJ
Glycobiology
2016[Jul]; 26
(7
): 772-783
PMID26911287
show ga
Defining how a glycan-binding protein (GBP) specifically selects its cognate
glycan from among the ensemble of glycans within the cellular glycome is an area
of intense study. Powerful insight into recognition mechanisms can be gained from
3D structures of GBPs complexed to glycans; however, such structures remain
difficult to obtain experimentally. Here an automated 3D structure generation
technique, called computational carbohydrate grafting, is combined with the
wealth of specificity information available from glycan array screening.
Integration of the array data with modeling and crystallography allows generation
of putative co-complex structures that can be objectively assessed and
iteratively altered until a high level of agreement with experiment is achieved.
Given an accurate model of the co-complexes, grafting is also able to discern
which binding determinants are active when multiple potential determinants are
present within a glycan. In some cases, induced fit in the protein or glycan was
necessary to explain the observed specificity, while in other examples a revised
definition of the minimal binding determinants was required. When applied to a
collection of 10 GBP-glycan complexes, for which crystallographic and array data
have been reported, grafting provided a structural rationalization for the
binding specificity of >90% of 1223 arrayed glycans. A webtool that enables
researchers to perform computational carbohydrate grafting is available at
www.glycam.org/gr (accessed 03 March 2016).