Hyaluronan: The Local Solution Conformation Determined by NMR and Computer Modeling is Close to a Contracted Left-handed 4-Fold Helix

Almond, Andrew; DeAngelis, Paul L.; Blundell, Charles

doi:10.1016/j.jmb.2006.02.077

Cited by 104 publications

(127 citation statements)

References 47 publications

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“…8 The GLYCAM06 method predicted w I in the CN 2 model to be 118 more negative than in the HA 2 model (u I was unaltered), which is in close agreement with this experimental data and similar to a previous simulation prediction 15 using the GLYCAM93 59 paramater set. Cluster analysis of the CN 2 and HA 2 trajectories supported this finding, the (approximate) experimentally observed 3D-structural perturbation caused by hexosamine 4-epimerization can be seen graphically to be reproduced in Figure 7A.…”

Section: Comparison Of Computed and Experimental Disaccharide Conformsupporting

confidence: 86%

“…Recent advances in isotopic labeling and material purification have facilitated determination of aqueous 3D-models for representative oligosaccharides in three of the four glycosaminoglycan sub-families (hyaluronan, 8 heparin, [9][10][11] and chondroitin/dermatan [12][13][14] ) by nuclear magnetic resonance (NMR) spectroscopy. Currently, however, only small glycosaminoglycan fragments are amenable to detailed NMR studies due to severe resonance overlap.…”

Section: Introductionmentioning

confidence: 99%

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Less is more when simulating unsulfated glycosaminoglycan 3D‐structure: Comparison of GLYCAM06/TIP3P, PM3‐CARB1/TIP3P, and SCC‐DFTB‐D/TIP3P predictions with experiment

Sattelle¹,

Almond²

2010

J Comput Chem

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The 3D-structure of extracellular matrix glycosaminoglycans is central to function, but is currently poorly understood. Resolving this will provide insight into their heterogeneous biological roles and help to realize their significant therapeutic potential. Glycosaminoglycan chemical isoforms are too numerous to study experimentally and simulation provides a tractable alternative. However, best practice for accurate calculation of glycosaminoglycan 3D-structure within biologically relevant nanosecond timescales is uncertain. Here, we evaluate the ability of three potentials to reproduce experimentally observed glycosaminoglycan monosaccharide puckering, disaccharide 3D-conformation, and characteristic solvent interactions. Temporal dynamics of unsulfated chondroitin, chondroitin-4-sulfate, and hyaluronan β(1→3) disaccharides were simulated within TIP3P explicit solvent unrestrained for 20 ns using the GLYCAM06 force-field and two semi-empirical quantum mechanics methods, PM3-CARB1 and SCC-DFTB-D (both within a hybrid QM/MM formalism). Comparison of calculated and experimental properties (vicinal couplings, nuclear Overhauser enhancements, and glycosidic linkage geometries) showed that the carbohydrate-specific parameterization of PM3-CARB1 imparted quantifiable benefits on monosaccharide puckering and that the SCC-DFTB-D method (including an empirical correction for dispersion) best modeled the effects of hexosamine 4-sulfation. However, paradoxically, the most approximate approach (GLYCAM06/TIP3P) was the best at predicting monosaccharide puckering, 3D-conformation, and solvent interactions. Our data contribute to the debate and emerging consensus on the relative performance of these levels of theory for biological molecules.

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Section: Comparison Of Computed and Experimental Disaccharide Conformsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Less is more when simulating unsulfated glycosaminoglycan 3D‐structure: Comparison of GLYCAM06/TIP3P, PM3‐CARB1/TIP3P, and SCC‐DFTB‐D/TIP3P predictions with experiment

Sattelle¹,

Almond²

2010

J Comput Chem

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“…Recent structural work in aqueous solution has suggested that an exchange between hydrogen bonds and water molecules is the preferred explanation. This leads to a locally dynamic structure that is on average a contracted fourfold helix in solution [14], which is similar to the sodium hyaluronate x-ray diffraction refinement performed under physiological conditions [9]. Rheological and scattering studies have concluded that HA chains are semiflexible in solution.…”

Section: Structural and Physical Studiessupporting

confidence: 65%

Hyaluronan

Almond

2007

Cell. Mol. Life Sci.

180

139

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The polysaccharide hyaluronan is an essential component of the vertebrate extracellular matrix and also produced by viruses, bacteria and fungi. Although the hyaluronan polymer is simply a disaccharide that repeats many thousands of times, it has an amazing array of biological functions and medical uses. For example, it is an efficient space filler that maintains hydration, serves as a substrate for assembly of proteoglycans and cellular locomotion, regulates cellular function and development, and is involved in tumor progression, inflammation and wound healing. Its physical properties and biocompatibility also make it of considerable importance in the development of engineered tissue, biomaterials and in clinical applications.

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“…Thus, several helical conformations of this polysaccharide (two-, three-and fourfold) have been observed. [6,7] As a principal constituent of the extracellular matrix, hyaluronic acid contributes significantly to cell proliferation and migration. By retaining a large amount of water, this polysaccharide is able to control tissue hydration.…”

Section: Introductionmentioning

confidence: 99%

Raman spectroscopic study on sodium hyaluronate: an effect of proton and γ irradiation

Synytsya

Alexa

et al. 2011

J Raman Spectroscopy

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Raman spectroscopy was applied to the analysis of structural changes in lyophilised sodium hyaluronate after proton and γ irradiation (0.5, 5, 50, 100, 200 and 600 Gy). Characteristic Raman bands of the polysaccharide were sensitive to irradiation. Significant damage was observed at doses of 50 Gy or higher. The spectral changes confirmed radiation-induced loss of native solution conformation, destruction of primary structure, fragmentation, cross-linking and elimination of functional groups. Differences in the effects of proton and γ radiation on sodium hyaluronate are discussed.

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Hyaluronan: The Local Solution Conformation Determined by NMR and Computer Modeling is Close to a Contracted Left-handed 4-Fold Helix

Cited by 104 publications

References 47 publications

Less is more when simulating unsulfated glycosaminoglycan 3D‐structure: Comparison of GLYCAM06/TIP3P, PM3‐CARB1/TIP3P, and SCC‐DFTB‐D/TIP3P predictions with experiment

Less is more when simulating unsulfated glycosaminoglycan 3D‐structure: Comparison of GLYCAM06/TIP3P, PM3‐CARB1/TIP3P, and SCC‐DFTB‐D/TIP3P predictions with experiment

Hyaluronan

Raman spectroscopic study on sodium hyaluronate: an effect of proton and γ irradiation

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