scholarly journals Discovery of Kasugamycin as a Potent Inhibitor of Glycoside Hydrolase Family 18 Chitinases

2021 ◽  
Vol 8 ◽  
Author(s):  
Huitang Qi ◽  
Xi Jiang ◽  
Yi Ding ◽  
Tian Liu ◽  
Qing Yang
Keyword(s):  
Glycoside Hydrolase ◽  
Potent Inhibitor ◽  
Aminoglycoside Antibiotic ◽  
Tryptophan Fluorescence ◽  
Competitive Inhibitor ◽  
Catalytic Triad ◽  
Microbial Pathogens ◽  
Glycoside Hydrolase Family ◽  
Similar Mode ◽  
Hydrolase Family

Kasugamycin, a well-known aminoglycoside antibiotic, has been used widely in agriculture and medicine to combat microbial pathogens by binding the ribosome to inhibit translation. Here, kasugamycin was discovered to be a competitive inhibitor of glycoside hydrolase family 18 (GH18) chitinases from three different organisms (bacterium, insect and human). Results from tryptophan fluorescence spectroscopy and molecular docking revealed that kasugamycin binds to the substrate-binding clefts in a similar mode as the substrate. An electrostatic interaction between the amino group of kasugamycin and the carboxyl group of a conserved aspartate in GH18 chitinase (one of the catalytic triad residues) was found to be vital for the inhibitory activity. This paper not only reports new molecular targets of kasugamycin, but also expands our thinking about GH inhibitor design by using a scaffold unrelated to the substrate.

scholarly journals A new group of glycoside hydrolase family 13 α-amylases with an aberrant catalytic triad

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Fean D. Sarian ◽  
Štefan Janeček ◽  
Tjaard Pijning ◽  
Ihsanawati ◽  
Zeily Nurachman ◽  
...  
Keyword(s):  
Glycoside Hydrolase ◽  
Catalytic Triad ◽  
Glycoside Hydrolase Family ◽  
Hydrolase Family ◽  
Glycoside Hydrolase Family 13

Xylanases of glycoside hydrolase family 30 – An overview

2021 ◽  
Vol 47 ◽  
pp. 107704
Author(s):  
Vladimír Puchart ◽  
Katarína Šuchová ◽  
Peter Biely
Keyword(s):  
Glycoside Hydrolase ◽  
Glycoside Hydrolase Family ◽  
Hydrolase Family ◽  
Glycoside Hydrolase Family 30

scholarly journals Modeled 3D-Structures of Proteobacterial Transglycosylases from Glycoside Hydrolase Family 17 Give Insight in Ligand Interactions Explaining Differences in Transglycosylation Products

2021 ◽  
Vol 11 (9) ◽  
pp. 4048
Author(s):  
Javier A. Linares-Pastén ◽  
Lilja Björk Jonsdottir ◽  
Gudmundur O. Hreggvidsson ◽  
Olafur H. Fridjonsson ◽  
Hildegard Watzlawick ◽  
...  
Keyword(s):  
Glycoside Hydrolase ◽  
Ligand Docking ◽  
Glycoside Hydrolase Family ◽  
Ligand Interactions ◽  
Tim Barrel ◽  
Branching Point ◽  
The Difference ◽  
Dynamics Simulations ◽  
And Function ◽  
Hydrolase Family

The structures of glycoside hydrolase family 17 (GH17) catalytic modules from modular proteins in the ndvB loci in Pseudomonas aeruginosa (Glt1), P. putida (Glt3) and Bradyrhizobium diazoefficiens (previously B. japonicum) (Glt20) were modeled to shed light on reported differences between these homologous transglycosylases concerning substrate size, preferred cleavage site (from reducing end (Glt20: DP2 product) or non-reducing end (Glt1, Glt3: DP4 products)), branching (Glt20) and linkage formed (1,3-linkage in Glt1, Glt3 and 1,6-linkage in Glt20). Hybrid models were built and stability of the resulting TIM-barrel structures was supported by molecular dynamics simulations. Catalytic amino acids were identified by superimposition of GH17 structures, and function was verified by mutagenesis using Glt20 as template (i.e., E120 and E209). Ligand docking revealed six putative subsites (−4, −3, −2, −1, +1 and +2), and the conserved interacting residues suggest substrate binding in the same orientation in all three transglycosylases, despite release of the donor oligosaccharide product from either the reducing (Glt20) or non-reducing end (Glt1, Gl3). Subsites +1 and +2 are most conserved and the difference in release is likely due to changes in loop structures, leading to loss of hydrogen bonds in Glt20. Substrate docking in Glt20 indicate that presence of covalently bound donor in glycone subsites −4 to −1 creates space to accommodate acceptor oligosaccharide in alternative subsites in the catalytic cleft, promoting a branching point and formation of a 1,6-linkage. The minimum donor size of DP5, can be explained assuming preferred binding of DP4 substrates in subsite −4 to −1, preventing catalysis.

scholarly journals Understanding the Polymerization Mechanism of Glycoside-Hydrolase Family 70 Glucansucrases

2006 ◽  
Vol 281 (42) ◽  
pp. 31254-31267
Author(s):  
Claire Moulis ◽  
Gilles Joucla ◽  
David Harrison ◽  
Emeline Fabre ◽  
Gabrielle Potocki-Veronese ◽  
...  
Keyword(s):  
Glycoside Hydrolase ◽  
Glycoside Hydrolase Family ◽  
Polymerization Mechanism ◽  
Hydrolase Family

scholarly journals Endo-fucoidan hydrolases from glycoside hydrolase family 107 (GH107) display structural and mechanistic similarities to α-l-fucosidases from GH29

2018 ◽  
Vol 293 (47) ◽  
pp. 18296-18308 ◽  
Author(s):  
Chelsea Vickers ◽  
Feng Liu ◽  
Kento Abe ◽  
Orly Salama-Alber ◽  
Meredith Jenkins ◽  
...  
Keyword(s):  
Glycoside Hydrolase ◽  
Biological Activities ◽  
Bacterial Species ◽  
Structural Data ◽  
Side Chain ◽  
Glycoside Hydrolase Family ◽  
X Ray Crystallography ◽  
Catalytic Mechanisms ◽  
Thickening Agents ◽  
Hydrolase Family

Fucoidans are chemically complex and highly heterogeneous sulfated marine fucans from brown macro algae. Possessing a variety of physicochemical and biological activities, fucoidans are used as gelling and thickening agents in the food industry and have anticoagulant, antiviral, antitumor, antibacterial, and immune activities. Although fucoidan-depolymerizing enzymes have been identified, the molecular basis of their activity on these chemically complex polysaccharides remains largely uninvestigated. In this study, we focused on three glycoside hydrolase family 107 (GH107) enzymes: MfFcnA and two newly identified members, P5AFcnA and P19DFcnA, from a bacterial species of the genus Psychromonas. Using carbohydrate-PAGE, we show that P5AFcnA and P19DFcnA are active on fucoidans that differ from those depolymerized by MfFcnA, revealing differential substrate specificity within the GH107 family. Using a combination of X-ray crystallography and NMR analyses, we further show that GH107 family enzymes share features of their structures and catalytic mechanisms with GH29 α-l-fucosidases. However, we found that GH107 enzymes have the distinction of utilizing a histidine side chain as the proposed acid/base catalyst in its retaining mechanism. Further interpretation of the structural data indicated that the active-site architectures within this family are highly variable, likely reflecting the specificity of GH107 enzymes for different fucoidan substructures. Together, these findings begin to illuminate the molecular details underpinning the biological processing of fucoidans.

scholarly journals Structure of a bacterial glycoside hydrolase family 63 enzyme in complex with its glycosynthase product, and insights into the substrate specificity

FEBS Journal ◽  
2013 ◽  
Vol 280 (18) ◽  
pp. 4560-4571 ◽  
Author(s):  
Takatsugu Miyazaki ◽  
Megumi Ichikawa ◽  
Gaku Yokoi ◽  
Motomitsu Kitaoka ◽  
Haruhide Mori ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Glycoside Hydrolase ◽  
Glycoside Hydrolase Family ◽  
Hydrolase Family

scholarly journals Substrate Specificity in Glycoside Hydrolase Family 10

2000 ◽  
Vol 275 (30) ◽  
pp. 23020-23026 ◽  
Author(s):  
Valérie Ducros ◽  
Simon J. Charnock ◽  
Urszula Derewenda ◽  
Zygmunt S. Derewenda ◽  
Zbigniew Dauter ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Glycoside Hydrolase ◽  
Glycoside Hydrolase Family ◽  
Glycoside Hydrolase Family 10 ◽  
Hydrolase Family

The α-glucuronidase Agu1 from Schizophyllum commune is a member of a novel glycoside hydrolase family (GH115)

2011 ◽  
Vol 90 (4) ◽  
pp. 1323-1332 ◽  
Author(s):  
Sun-Li Chong ◽  
Evy Battaglia ◽  
Pedro M. Coutinho ◽  
Bernard Henrissat ◽  
Maija Tenkanen ◽  
...  
Keyword(s):  
Glycoside Hydrolase ◽  
Schizophyllum Commune ◽  
Glycoside Hydrolase Family ◽  
Hydrolase Family
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