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Hung-wen Liu - One of the best experts on this subject based on the ideXlab platform.
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Identification of the Formycin A Biosynthetic Gene Cluster from Streptomyces kaniharaensis Illustrates the Interplay between Biological Pyrazolopyrimidine Formation and de Novo Purine Biosynthesis.
Journal of the American Chemical Society, 2019Co-Authors: Shao-an Wang, Jia Zeng, Yujie Geng, Daan Ren, Yasushi Ogasawara, Seema Irani, Yan Zhang, Hung-wen LiuAbstract:Formycin A is a potent purine nucleoside antibiotic with a C-Glycosidic Linkage between the ribosyl moiety and the pyrazolopyrimidine base. Herein, a cosmid is identified from the Streptomyces kaniharaensis genome library that contains the for gene cluster responsible for the biosynthesis of formycin. Subsequent gene deletion experiments and in vitro characterization of the forBCH gene products established their catalytic functions in formycin biosynthesis. Results also demonstrated that PurH from de novo purine biosynthesis plays a key role in pyrazolopyrimidine formation during biosynthesis of formycin A. The participation of PurH in both pathways represents a good example of how primary and secondary metabolism are interlinked.
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Identification of the Formycin A Biosynthetic Gene Cluster from Streptomyces kaniharaensis Illustrates the Interplay between Biological Pyrazolopyrimidine Formation and de Novo Purine Biosynthesis
2019Co-Authors: Shao-an Wang, Jia Zeng, Yujie Geng, Daan Ren, Yasushi Ogasawara, Seema Irani, Yan Zhang, Hung-wen LiuAbstract:Formycin A is a potent purine nucleoside antibiotic with a C-Glycosidic Linkage between the ribosyl moiety and the pyrazolopyrimidine base. Herein, a cosmid is identified from the Streptomyces kaniharaensis genome library that contains the for gene cluster responsible for the biosynthesis of formycin. Subsequent gene deletion experiments and in vitro characterization of the forBCH gene products established their catalytic functions in formycin biosynthesis. Results also demonstrated that PurH from de novo purine biosynthesis plays a key role in pyrazolopyrimidine formation during biosynthesis of formycin A. The participation of PurH in both pathways represents a good example of how primary and secondary metabolism are interlinked
Goran Widmalm - One of the best experts on this subject based on the ideXlab platform.
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delineating the conformational flexibility of trisaccharides from nmr spectroscopy experiments and computer simulations
Physical Chemistry Chemical Physics, 2016Co-Authors: Mingjun Yang, Goran Widmalm, Thibault Angles Dortoli, Elin Sawen, Madhurima Jana, Alexander D MackerellAbstract:The conformation of saccharides in solution is challenging to characterize in the context of a single well-defined three-dimensional structure. Instead, they are better represented by an ensemble of conformations associated with their structural diversity and flexibility. In this study, we delineate the conformational heterogeneity of five trisaccharides via a combination of experimental and computational techniques. Experimental NMR measurements target conformationally sensitive parameters, including J couplings and effective distances around the Glycosidic Linkages, while the computational simulations apply the well-calibrated additive CHARMM carbohydrate force field in combination with efficient enhanced sampling molecular dynamics simulation methods. Analysis of conformational heterogeneity is performed based on sampling of discreet states as defined by dihedral angles, on root-mean-square differences of Cartesian coordinates and on the extent of volume sampled. Conformational clustering, based on the Glycosidic Linkage dihedral angles, shows that accounting for the full range of sampled conformations is required to reproduce the experimental data, emphasizing the utility of the molecular simulations in obtaining an atomic detailed description of the conformational properties of the saccharides. Results show the presence of differential conformational preferences as a function of primary sequence and Glycosidic Linkage types. Significant differences in conformational ensembles associated with the anomeric configuration of a single Glycosidic Linkage reinforce the impact of such changes on the conformational properties of carbohydrates. The present structural insights of the studied trisaccharides represent a foundation for understanding the range of conformations adopted in larger oligosaccharides and how these molecules encode their conformational heterogeneity into the monosaccharide sequence.
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flexibility at a Glycosidic Linkage revealed by molecular dynamics stochastic modeling and 13c nmr spin relaxation conformational preferences of α l rhap α 1 2 α l rhap ome in water and dimethyl sulfoxide solutions
Physical Chemistry Chemical Physics, 2016Co-Authors: Robert Pendrill, Olof Engstrom, Andrea Volpato, Mirco Zerbetto, Antonino Polimeno, Goran WidmalmAbstract:The monosaccharide L-rhamnose is common in bacterial polysaccharides and the disaccharide α-L-Rhap-α-(1 → 2)-α-L-Rhap-OMe represents a structural model for a part of Shigella flexneri O-antigen polysaccharides. Utilization of [1′-13C]-site-specific labeling in the anomeric position at the Glycosidic Linkage between the two sugar residues facilitated the determination of transGlycosidic NMR 3JCH and 3JCC coupling constants. Based on these spin–spin couplings the major state and the conformational distribution could be determined with respect to the ψ torsion angle, which changed between water and dimethyl sulfoxide (DMSO) as solvents, a finding mirrored by molecular dynamics (MD) simulations with explicit solvent molecules. The 13C NMR spin relaxation parameters T1, T2, and heteronuclear NOE of the probe were measured for the disaccharide in DMSO-d6 at two magnetic field strengths, with standard deviations ≤1%. The combination of MD simulation and a stochastic description based on the diffusive chain model resulted in excellent agreement between calculated and experimentally observed 13C relaxation parameters, with an average error of <2%. The coupling between the global reorientation of the molecule and the local motion of the spin probe is deemed essential if reproduction of NMR relaxation parameters should succeed, since decoupling of the two modes of motion results in significantly worse agreement. Calculation of 13C relaxation parameters based on the correlation functions obtained directly from the MD simulation of the solute molecule in DMSO as solvent showed satisfactory agreement with errors on the order of 10% or less.
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structural studies of the o antigen polysaccharide from the enteroinvasive escherichia coli o173
Carbohydrate Research, 1999Co-Authors: Malin Linnerborg, Andrej Weintraub, Goran WidmalmAbstract:The structure of the O-antigen polysaccharide (PS) from Escherichia coli O173 has been investigated. Sugar and methylation analyses, electrospray ionisation mass spectrometry together with 1H, 31P and 13C NMR spectroscopy were the main methods used. The structure of the pentasaccharide repeating unit of the PS was found to be: [formula: see text] By treatment with 48% HF the phosphoric diester Linkage was cleaved together with the Glycosidic Linkage of the fucosyl group, rendering a tetrasaccharide with the structure: alpha-D-Glcp-(1-->2)-beta-D-Glcp-(1-->3)-beta-D-GlcpNAc-(1-->3)-D-Glc.
Shao-an Wang - One of the best experts on this subject based on the ideXlab platform.
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Identification of the Formycin A Biosynthetic Gene Cluster from Streptomyces kaniharaensis Illustrates the Interplay between Biological Pyrazolopyrimidine Formation and de Novo Purine Biosynthesis.
Journal of the American Chemical Society, 2019Co-Authors: Shao-an Wang, Jia Zeng, Yujie Geng, Daan Ren, Yasushi Ogasawara, Seema Irani, Yan Zhang, Hung-wen LiuAbstract:Formycin A is a potent purine nucleoside antibiotic with a C-Glycosidic Linkage between the ribosyl moiety and the pyrazolopyrimidine base. Herein, a cosmid is identified from the Streptomyces kaniharaensis genome library that contains the for gene cluster responsible for the biosynthesis of formycin. Subsequent gene deletion experiments and in vitro characterization of the forBCH gene products established their catalytic functions in formycin biosynthesis. Results also demonstrated that PurH from de novo purine biosynthesis plays a key role in pyrazolopyrimidine formation during biosynthesis of formycin A. The participation of PurH in both pathways represents a good example of how primary and secondary metabolism are interlinked.
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Identification of the Formycin A Biosynthetic Gene Cluster from Streptomyces kaniharaensis Illustrates the Interplay between Biological Pyrazolopyrimidine Formation and de Novo Purine Biosynthesis
2019Co-Authors: Shao-an Wang, Jia Zeng, Yujie Geng, Daan Ren, Yasushi Ogasawara, Seema Irani, Yan Zhang, Hung-wen LiuAbstract:Formycin A is a potent purine nucleoside antibiotic with a C-Glycosidic Linkage between the ribosyl moiety and the pyrazolopyrimidine base. Herein, a cosmid is identified from the Streptomyces kaniharaensis genome library that contains the for gene cluster responsible for the biosynthesis of formycin. Subsequent gene deletion experiments and in vitro characterization of the forBCH gene products established their catalytic functions in formycin biosynthesis. Results also demonstrated that PurH from de novo purine biosynthesis plays a key role in pyrazolopyrimidine formation during biosynthesis of formycin A. The participation of PurH in both pathways represents a good example of how primary and secondary metabolism are interlinked
Shu-hua Lee - One of the best experts on this subject based on the ideXlab platform.
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Crystal structure of truncated Fibrobacter succinogenes 1,3-1,4-beta-D-glucanase in complex with beta-1,3-1,4-cellotriose.
Journal of molecular biology, 2005Co-Authors: Li-chu Tsai, Lie-fen Shyur, Yi-sheng Cheng, Shu-hua LeeAbstract:Fibrobacter succinogenes 1,3-1,4-beta-D-glucanase (Fsbeta-glucanase) catalyzes the specific hydrolysis of beta-1,4 Glycosidic bonds adjacent to beta-1,3 Linkages in beta-D-glucans or lichenan. This is the first report to elucidate the crystal structure of a truncated Fsbeta-glucanase (TFsbeta-glucanase) in complex with beta-1,3-1,4-cellotriose, a major product of the enzyme reaction. The crystal structures, at a resolution of 2.3 angstroms, reveal that the overall fold of TFsbeta-glucanase remains virtually unchanged upon sugar binding. The enzyme accommodates five glucose residues, forming a concave active cleft. The beta-1,3-1,4-cellotriose with subsites -3 to -1 bound to the active cleft of TFsbeta-glucanase with its reducing end subsite -1 close to the key catalytic residues Glu56 and Glu60. All three subsites of the beta-1,3-1,4-cellotriose adopted a relaxed C(1)4 conformation, with a beta-1,3 Glycosidic Linkage between subsites -2 and -1, and a beta-1,4 Glycosidic Linkage between subsites -3 and -2. On the basis of the enzyme-product complex structure observed in this study, a catalytic mechanism and substrate binding conformation of the active site of TFsbeta-glucanase is proposed.
Anita Plazinska - One of the best experts on this subject based on the ideXlab platform.
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ring inversion properties of 1 2 1 3 and 1 6 linked hexopyranoses and their correlation with the conformation of Glycosidic Linkages
Carbohydrate Research, 2016Co-Authors: Wojciech Plazinski, Mateusz Drach, Anita PlazinskaAbstract:Abstract Enhanced-sampling molecular dynamics simulations performed within the GROMOS 56a6 CARBO_R force field were applied in order to elucidate ring-inversion properties of hexopyranose residues in a chain for the case of α(1→ n ) and β(1→ n ) Glycosidic Linkages ( n = 2, 3 or 6). The results indicate that ring-inversion free energies calculated for residues in a chain are weakly correlated with those of corresponding monomers, except of the case of 1→6 Linkages. This, in combination with the results for O 1 -methyl-hexopyranosides (Plazinski et al, 2016), suggests that both the type of functionalization (glycolysation vs. methylation) and the topology of Glycosidic Linkage play an important role in possible alterations of the hexopyranose ring flexibility. Additionally, the correlation of the ring shape with the preferred geometry of Glycosidic Linkages was investigated. The Linkages of the 1→2, 1→3 and 1→6 types do not follow the trend found in the case of the 1→4 Linkages, i.e. there is no correlation between the range of changes in the Glycosidic Linkage conformation and the topological orientation of the Glycosidic oxygen atoms. Overall, the ring shape affects the Glycosidic Linkages of the 1→6 type to the least extent in comparison to the remaining ones.