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Insights into Furanose Solution Conformations: Beyond the Two-State Model

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A two-state model is commonly used for interpreting ring conformations of furanoses based on NMR scalar 3J-coupling constants, with the ring populating relatively narrow distributions in the North and the South of the pseudorotation itinerary. The validity of this simple approach has been questioned, and is examined here in detail employing molecular dynamics (MD) simulations with a new GLYCAM force field parameter set for furanoses. Theoretical 3J-coupling constants derived from unrestrained MD simulations with the new furanose-specific parameters agreed with the experimental coupling constants to within 1 Hz on average. The results confirm that a two state model is a reasonable description for the ring conformation in the majority of methyl furanosides. However, in the case of methyl α-D-arabinofuranoside the ring populates a continuum of states from North to South via the eastern side of the pseudorotational itinerary. Two key properties are responsible for these differences. Firstly, East and West regions in β- and α-anomers, respectively, are destabilized by the absence of the anomeric effect. And, secondly, East or West conformations can be further destabilized by repulsive interactions among vicinal hydroxyl groups and ring oxygen atoms when the vicinal hydroxyl groups are in syn-configurations (such as in ribose and lyxose) more so than when in anti (arabinose, xylose).
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ARTICLE
Insights into furanose solution conformations: beyond the two-
state model
Xiaocong Wang
1
Robert J. Woods
1
Received: 11 December 2015 / Accepted: 8 March 2016 / Published online: 12 March 2016
ÓSpringer Science+Business Media Dordrecht 2016
Abstract A two-state model is commonly used for
interpreting ring conformations of furanoses based on
NMR scalar
3
J-coupling constants, with the ring populating
relatively narrow distributions in the North and the South
of the pseudorotation itinerary. The validity of this simple
approach has been questioned, and is examined here in
detail employing molecular dynamics (MD) simulations
with a new GLYCAM force field parameter set for fura-
noses. Theoretical
3
J-coupling constants derived from
unrestrained MD simulations with the new furanose-
specific parameters agreed with the experimental coupling
constants to within 1 Hz on average. The results confirm
that a two state model is a reasonable description for the
ring conformation in the majority of methyl furanosides.
However, in the case of methyl a-D-arabinofuranoside the
ring populates a continuum of states from North to South
via the eastern side of the pseudorotational itinerary. Two
key properties are responsible for these differences. Firstly,
East and West regions in b- and a-anomers, respectively,
are destabilized by the absence of the anomeric effect. And,
secondly, East or West conformations can be further
destabilized by repulsive interactions among vicinal
hydroxyl groups and ring oxygen atoms when the vicinal
hydroxyl groups are in syn-configurations (such as in ribose
and lyxose) more so than when in anti (arabinose, xylose).
Keywords Pseudorotation Anomeric effect Potential
energy surface Molecular dynamics simulation
GLYCAM AMBER
Introduction
Furanoses are essential components in the backbone of
nucleic acids (RNA and DNA) and are also frequent
components of complex polysaccharides found in organ-
isms ranging from bacteria to protozoa, fungi and plants
(Taha et al. 2013). Their conformational properties affect
the structure and recognition of the polymers in which they
are found. In marked contrast to six-membered sugar rings
(pyranoses), the five-membered forms (furanoses) exhibit a
high level of internal ring flexing (Bartenev et al. 1987;
Levitt and Warshel 1978; Seo et al. 2008). As a result,
furanoses can interconvert between multiple ring confor-
mations (Houseknecht et al. 2003a), whereas pyranoses are
usually found in single, energy-favorable chair conforma-
tion (Angyal 1984). This feature of furanoses greatly
complicates the development and interpretation of struc-
ture–function relationships for these small but crucial
molecules.
The conformational analysis of ring conformations of
carbohydrates molecules in solution relies heavily on
deconvoluting NMR scalar
3
J-coupling constants into ring
puckering geometries and populations (De Leeuw and
Altona 1983; Padrta and Sklenar 2002; Sun et al. 2004). In
the case of furanoses, interpreting their conformational
populations from
3
J-coupling constants typically requires
assumptions regarding to the number of states that are
present. In the two-state model introduced by Altona and
Sundaral (1972) to interpret the ring conformations of the
ribofuranosyl ring in nucleic acids, it is assumed that the
Electronic supplementary material The online version of this
article (doi:10.1007/s10858-016-0028-y) contains supplementary
material, which is available to authorized users.
&Robert J. Woods
rwoods@ccrc.uga.edu
1
Complex Carbohydrate Research Center, University of
Georgia, Athens, GA 30602, USA
123
J Biomol NMR (2016) 64:291–305
DOI 10.1007/s10858-016-0028-y
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... Five-carbon furanose rings are notoriously more flexible and thermodynamically less stable than their six-carbon counterparts, meaning that unlike pyranoses, furanoses can interconvert between different ring conformations. This reflects similar energy states for the different conformations, [38,39] a feature that significantly complicates the organic synthesis of furanosides. Since catalysis mediated by any given GH involves a specific conformational itinerary for the donor substrate, the lowered energy barriers between furanoside conformations [38] implies that furanosidase-catalysed reactions display altered mechanisms when compared to those catalysed by pyranosidases, and GH51 α-L-arabinofuranosidases have been predicted to present [E3] ǂ transition states along their conformational itinerary ( 4 E → [E3] ǂ → 2 E → [E3] ǂ → E 3 / 4 T3). ...
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