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231224s2016 xx |||||o 00| ||eng c |
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|a 10.1002/jcc.24306
|2 doi
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|a pubmed25n0856.xml
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|a DE-627
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|c DE-627
|e rakwb
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|a eng
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|a Zhang, Xin
|e verfasserin
|4 aut
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|a Combined QM(DFT)/MM molecular dynamics simulations of the deamination of cytosine by yeast cytosine deaminase (yCD)
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|c 2016
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|a Text
|b txt
|2 rdacontent
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|a ƒaComputermedien
|b c
|2 rdamedia
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|a ƒa Online-Ressource
|b cr
|2 rdacarrier
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|a Date Completed 20.08.2018
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|a Date Revised 20.08.2018
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a © 2016 Wiley Periodicals, Inc.
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|a Extensive combined quantum mechanical (B3LYP/6-31G*) and molecular mechanical (QM/MM) molecular dynamics simulations have been performed to elucidate the hydrolytic deamination mechanism of cytosine to uracil catalyzed by the yeast cytosine deaminase (yCD). Though cytosine has no direct binding to the zinc center, it reacts with the water molecule coordinated to zinc, and the adjacent conserved Glu64 serves as a general acid/base to shuttle protons from water to cytosine. The overall reaction consists of several proton-transfer processes and nucleophilic attacks. A tetrahedral intermediate adduct of cytosine and water binding to zinc is identified and similar to the crystal structure of yCD with the inhibitor 2-pyrimidinone. The rate-determining step with the barrier of 18.0 kcal/mol in the whole catalytic cycle occurs in the process of uracil departure where the proton transfer from water to Glu64 and nucleophilic attack of the resulting hydroxide anion to C2 of the uracil ring occurs synchronously. © 2016 Wiley Periodicals, Inc
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|a Journal Article
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|a Research Support, Non-U.S. Gov't
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|a Research Support, U.S. Gov't, Non-P.H.S.
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|a DFT
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|a combined QM/MM
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|a cytosine
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|a enzymatic catalysis
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|a molecular dynamics
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|a Cytosine
|2 NLM
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|a 8J337D1HZY
|2 NLM
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|a Cytosine Deaminase
|2 NLM
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|a EC 3.5.4.1
|2 NLM
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| 700 |
1 |
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|a Zhao, Yuan
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Yan, Honggao
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Cao, Zexing
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Mo, Yirong
|e verfasserin
|4 aut
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| 773 |
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|i Enthalten in
|t Journal of computational chemistry
|d 1984
|g 37(2016), 13 vom: 15. Mai, Seite 1163-74
|w (DE-627)NLM098138448
|x 1096-987X
|7 nnas
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| 773 |
1 |
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|g volume:37
|g year:2016
|g number:13
|g day:15
|g month:05
|g pages:1163-74
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|u http://dx.doi.org/10.1002/jcc.24306
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