TRNKA, Tomáš, Stanislav KOZMON, Igor TVAROŠKA a Jaroslav KOČA. Quantum-chemical insight into the reaction mechanism of polypeptide UDP-GalNAc transferase 2, a retaining glycosyltransferase. In X Discussions in Structural Molecular Biology. ISSN 1211-5894. 2012.
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Základní údaje
Originální název Quantum-chemical insight into the reaction mechanism of polypeptide UDP-GalNAc transferase 2, a retaining glycosyltransferase
Autoři TRNKA, Tomáš, Stanislav KOZMON, Igor TVAROŠKA a Jaroslav KOČA.
Vydání X Discussions in Structural Molecular Biology, 2012.
Další údaje
Originální jazyk angličtina
Typ výsledku Konferenční abstrakta
Obor Fyzikální chemie a teoretická chemie
Stát vydavatele Česká republika
Utajení není předmětem státního či obchodního tajemství
WWW URL
Organizace Přírodovědecká fakulta – Masarykova univerzita – Repozitář
ISSN 1211-5894
Klíčová slova anglicky glycosyltransferase; QM/MM; quantum chemistry; reaction mechanism; transition state
Návaznosti ED1.1.00/02.0068, projekt VaV. 286154, interní kód Repo.
Změnil Změnil: RNDr. Daniel Jakubík, učo 139797. Změněno: 6. 4. 2013 00:50.
Anotace
Protein glycosylation is thought to be main means of cell recognition. Misregulation of the cascade of glycosyltransferases is related to many diseases with the most prominent example being cancer. There is thus significant scientific interest in the reaction mechanisms of glycosyltransferases. However, reaction mechanism of the configuration-retaining group of glycosyltransferases hasn't been explained yet. For his reason we have chosen a retaining glycosyltransferase – polypeptide UDP-GalNAc transferase (ppGalNAcT) – as the subject of our quantum-chemical study. This enzyme catalyses the transfer of N-acetylgalactosamine moiety onto protein serine or threonine hydroxyls, forming the first bond of the so-called O-linked glycosylation pathway. Increased activity of this enzyme has been found to enable metastasis of breast and colorectal cancer.Thanks to the availability of high-resolution X-ray structures of three members of the ppGalNAcT family (human transferases 2 and 10, murine transferase 1) we have been able to successfully mount a quantum chemistry study of the human ppGalNAcT2, leveraging information on substrate positioning in active site from the ppGalNAcT10. We are using a hybrid quantum mechanics/molecular mechanics approach using density functional theory on the BP86/TZP level for the important part of the active site. Structures in reactant and product energy minima have been successfully obtained, enabling a potential energy surface scan to find the locations of transition state candidates. Results clearly show that proton transfer between the acceptor hydroxyl moiety and the donor phosphate plays a crucial role in enabling the reaction to take place. The 2D energy map suggests that the reaction proceeds via a two-step mechanism with formation of a carbocation intermediate and its subsequent nucleophilic trapping by the acceptor oxygen. However, exact location of the transition states is yet necessary to prove this conclusively.
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poster_ppGalNAcT_scan.pdf Licence Creative Commons  Verze souboru 6. 4. 2013

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poster_ppGalNAcT_scan.pdf
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https://repozitar.cz/auth/repo/16229/88887/
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https://repozitar.cz/repo/16229/88887/
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https://repozitar.cz/auth/repo/16229/88887/?info
Ze světa do Správce
https://repozitar.cz/repo/16229/88887/?info
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So 6. 4. 2013 00:50

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  • osoba RNDr. Daniel Jakubík, uco 139797
  • osoba Mgr. Ľuboš Lunter, uco 143320
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Přidat do schránky Zobrazeno: 28. 3. 2024 16:17