Computational study of β-N-acetylhexosaminidase from Talaromyces flavus, a glycosidase with high substrate flexibility

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F67179843%3A_____%2F15%3A00444137" target="_blank" >RIV/67179843:_____/15:00444137 - isvavai.cz</a>

Alternative codes found

RIV/61388971:_____/15:00444137

Result on the web

<a href="http://dx.doi.org/10.1186/s12859-015-0465-8" target="_blank" >http://dx.doi.org/10.1186/s12859-015-0465-8</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1186/s12859-015-0465-8" target="_blank" >10.1186/s12859-015-0465-8</a>

Result language

angličtina

Original language name

Computational study of β-N-acetylhexosaminidase from Talaromyces flavus, a glycosidase with high substrate flexibility

Original language description

Background β-N-Acetylhexosaminidase (GH20) from the filamentous fungus Talaromyces flavus, previously identified as a prominent enzyme in the biosynthesis of modified glycosides, lacks a high resolution three-dimensional structure so far. Despite of high sequence identity to previously reported Aspergillus oryzae and Penicilluim oxalicum β-N-acetylhexosaminidases, this enzyme tolerates significantly better substrate modification. Understanding of key structural features, prediction of effective mutants and potential substrate characteristics prior to their synthesis are of general interest. Results Computational methods including homology modeling and molecular dynamics simulations were applied to shad light on the structure-activity relationship in the enzyme. Primary sequence analysis revealed some variable regions able to influence difference in substrate affinity of hexosaminidases. Moreover, docking in combination with consequent molecular dynamics simulations of C-6 modified glycosides enabled us to identify the structural features required for accommodation and processing of these bulky substrates in the active site of hexosaminidase from T. flavus. To access the reliability of predictions on basis of the reported model, all results were confronted with available experimental data that demonstrated the principal correctness of the predictions as well as the model. Conclusions The main variable regions in β-N-acetylhexosaminidases determining difference in modified substrate affinity are located close to the active site entrance and engage two loops. Differences in primary sequence and the spatial arrangement of these loops and their interplay with active site amino acids, reflected by interaction energies and dynamics, account for the different catalytic activity and substrate specificity of the various fungal and bacterial β-N-acetylhexosaminidases.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

EE - Microbiology, virology

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2015

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

B M C Bioinformatics

ISSN

1471-2105

e-ISSN

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Volume of the periodical

16

Issue of the periodical within the volume

JAN

Country of publishing house

GB - UNITED KINGDOM

Number of pages

15

Pages from-to

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UT code for WoS article

000354554900001

EID of the result in the Scopus database

2-s2.0-84926288614