Three-dimensional homology model of GlcNAc-TV
glycosyltransferase

J 2016

Three-dimensional homology model of GlcNAc-TV glycosyltransferase

JANOŠ, Pavel, Stanislav KOZMON, Igor TVAROŠKA and Jaroslav KOČA

Basic information

Original name

Three-dimensional homology model of GlcNAc-TV glycosyltransferase

Authors

JANOŠ, Pavel (203 Czech Republic, belonging to the institution), Stanislav KOZMON (703 Slovakia, belonging to the institution), Igor TVAROŠKA (703 Slovakia, belonging to the institution) and Jaroslav KOČA (203 Czech Republic, guarantor, belonging to the institution)

Edition

Glycobiology, Oxford University Press, 2016, 0959-6658

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10600 1.6 Biological sciences

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 3.112

RIV identification code

RIV/00216224:14310/16:00089828

Organization unit

Faculty of Science

DOI

http://dx.doi.org/10.1093/glycob/cww010

UT WoS

000384766000009

Keywords in English

GlcNAc-TV; glycosyltransferase; homology model; N-glycosylation

Abstract

V originále

The enzyme UDP-N-acetylglucosamine: a-d-mannoside b-1-6 N-acetylglucosaminyltransferase V (GnT-V) catalyzes the transfer of GlcNAc from the UDP-GlcNAc donor to the a-1-6-linked mannose of the trimannosyl core structure of glycoproteins to produce the b-1-6-linked branching of N-linked oligosaccharides. b-1-6-GlcNAc-branched N-glycans are associated with cancer growth and metastasis. Therefore, the inhibition of GnT-V represents a key target for anti-cancer drug development. However, the development of potent and specific inhibitors of GnT-V is hampered by the lack of information on the three-dimensional structure of the enzyme and on the binding characteristics of its substrates. Here we present the first 3D structure of GnT-V as a result of homology modeling. Various alignment methods, docking the donor and acceptor substrates, and molecular dynamics simulation were used to construct seven homology models of GnT-V and characterize the binding of its substrates. The best homology model is consistent with available experimental data. The three-dimensional model, the structure of the enzyme catalytic site and binding information obtained for the donor and acceptor can be useful in studies of the catalytic mechanism and design of inhibitors of GnT-V.

Links

ED1.1.00/02.0068, research and development project

Name: CEITEC - central european institute of technology

LH13055, research and development project

Name: Multidisciplinární přístup k návrhu léčiv - Inhibice proteinů s návazností na cukry (Acronym: MADICA)

Investor: Ministry of Education, Youth and Sports of the CR

Citovat

JANOŠ, Pavel, Stanislav KOZMON, Igor TVAROŠKA and Jaroslav KOČA. Three-dimensional homology model of GlcNAc-TV glycosyltransferase. Glycobiology. Oxford University Press, 2016, vol. 26, No 7, p. 757-771. ISSN 0959-6658. Available from: https://dx.doi.org/10.1093/glycob/cww010.

@article{1344264,
   author = {Janoš, Pavel and Kozmon, Stanislav and Tvaroška, Igor and Koča, Jaroslav},
   article_number = {7},
   doi = {http://dx.doi.org/10.1093/glycob/cww010},
   keywords = {GlcNAc-TV; glycosyltransferase; homology model; N-glycosylation},
   language = {eng},
   issn = {0959-6658},
   journal = {Glycobiology},
   title = {Three-dimensional homology model of GlcNAc-TV glycosyltransferase},
   url = {http://dx.doi.org/10.1093/glycob/cww010},
   volume = {26},
   year = {2016}
}

TY  - JOUR
ID  - 1344264
AU  - Janoš, Pavel - Kozmon, Stanislav - Tvaroška, Igor - Koča, Jaroslav
PY  - 2016
TI  - Three-dimensional homology model of GlcNAc-TV glycosyltransferase
JF  - Glycobiology
VL  - 26
IS  - 7
SP  - 757-771
EP  - 757-771
PB  - Oxford University Press
SN  - 09596658
KW  - GlcNAc-TV
KW  - glycosyltransferase
KW  - homology model
KW  - N-glycosylation
UR  - http://dx.doi.org/10.1093/glycob/cww010
L2  - http://dx.doi.org/10.1093/glycob/cww010
N2  - The enzyme UDP-N-acetylglucosamine: a-d-mannoside b-1-6 N-acetylglucosaminyltransferase V (GnT-V) catalyzes the transfer of GlcNAc from the UDP-GlcNAc donor to the a-1-6-linked mannose of the trimannosyl core structure of glycoproteins to produce the b-1-6-linked branching of N-linked oligosaccharides. b-1-6-GlcNAc-branched N-glycans are associated with cancer growth and metastasis. Therefore, the inhibition of GnT-V represents a key target for anti-cancer drug development. However, the development of potent and specific inhibitors of GnT-V is hampered by the lack of information on the three-dimensional structure of the enzyme and on the binding characteristics of its substrates. Here we present the first 3D structure of GnT-V as a result of homology modeling. Various alignment methods, docking the donor and acceptor substrates, and molecular dynamics simulation were used to construct seven homology models of GnT-V and characterize the binding of its substrates. The best homology model is consistent with available experimental data. The three-dimensional model, the structure of the enzyme catalytic site and binding information obtained for the donor and acceptor can be useful in studies of the catalytic mechanism and design of inhibitors of GnT-V.
ER  -

JANOŠ, Pavel, Stanislav KOZMON, Igor TVAROŠKA and Jaroslav KOČA. Three-dimensional homology model of GlcNAc-TV glycosyltransferase. \textit{Glycobiology}. Oxford University Press, 2016, vol.~26, No~7, p.~757-771. ISSN~0959-6658. Available from: https://dx.doi.org/10.1093/glycob/cww010.

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