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Catalysis of carboxypeptidase A: promoted-water versus nucleophilic pathways

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Catalysis of carboxypeptidase A : promoted-water versus nucleophilic pathways. / Wu, Shanshan; Zhang, Chunchun; Xu, Dingguo; Guo, Hua.

I: Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical, Bind 114, Nr. 28, 2010, s. 9259-9267.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Wu, S, Zhang, C, Xu, D & Guo, H 2010, 'Catalysis of carboxypeptidase A: promoted-water versus nucleophilic pathways', Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical, bind 114, nr. 28, s. 9259-9267. https://doi.org/10.1021/jp101448j

APA

Wu, S., Zhang, C., Xu, D., & Guo, H. (2010). Catalysis of carboxypeptidase A: promoted-water versus nucleophilic pathways. Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical, 114(28), 9259-9267. https://doi.org/10.1021/jp101448j

Vancouver

Wu S, Zhang C, Xu D, Guo H. Catalysis of carboxypeptidase A: promoted-water versus nucleophilic pathways. Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical. 2010;114(28):9259-9267. https://doi.org/10.1021/jp101448j

Author

Wu, Shanshan ; Zhang, Chunchun ; Xu, Dingguo ; Guo, Hua. / Catalysis of carboxypeptidase A : promoted-water versus nucleophilic pathways. I: Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical. 2010 ; Bind 114, Nr. 28. s. 9259-9267.

Bibtex

@article{428be687e85f47f2aaf41240c446a997,
title = "Catalysis of carboxypeptidase A: promoted-water versus nucleophilic pathways",
abstract = "The catalytic mechanism of carboxypeptidase A (CPA) for the hydrolysis of ester substrates is investigated using hybrid quantum mechanical/molecular mechanical (QM/MM) methods and high-level density functional theory. The prevailing mechanism was found to utilize an active-site water molecule assisted by Glu270, and this so-called promoted-water pathway is similar to that in the CPA catalyzed proteolytic reaction (D. Xu and H. Guo, J. Am. Chem. Soc. 2009, 131, 9780). On the other hand, our simulations indicated the existence of an alternative pathway due to direct nucleophilic attack of Glu270 on the scissile carbonyl carbon. This so-called nucleophilic pathway, which is not viable in proteolytic reactions, leads to a stable acyl-enzyme complex. However, the nucleophilic pathway is nonproductive as it is blocked by a high barrier in the deacylation step. On the basis of results reported here and in our earlier publication, a unified model is proposed to account for nearly all experimental observations concerning the catalysis of CPA.",
keywords = "Biocatalysis, Carboxypeptidases A, Catalytic Domain, Hydrolysis, Quantum Theory, Thermodynamics, Water",
author = "Shanshan Wu and Chunchun Zhang and Dingguo Xu and Hua Guo",
year = "2010",
doi = "10.1021/jp101448j",
language = "English",
volume = "114",
pages = "9259--9267",
journal = "Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical",
issn = "1520-6106",
publisher = "American Chemical Society",
number = "28",

}

RIS

TY - JOUR

T1 - Catalysis of carboxypeptidase A

T2 - promoted-water versus nucleophilic pathways

AU - Wu, Shanshan

AU - Zhang, Chunchun

AU - Xu, Dingguo

AU - Guo, Hua

PY - 2010

Y1 - 2010

N2 - The catalytic mechanism of carboxypeptidase A (CPA) for the hydrolysis of ester substrates is investigated using hybrid quantum mechanical/molecular mechanical (QM/MM) methods and high-level density functional theory. The prevailing mechanism was found to utilize an active-site water molecule assisted by Glu270, and this so-called promoted-water pathway is similar to that in the CPA catalyzed proteolytic reaction (D. Xu and H. Guo, J. Am. Chem. Soc. 2009, 131, 9780). On the other hand, our simulations indicated the existence of an alternative pathway due to direct nucleophilic attack of Glu270 on the scissile carbonyl carbon. This so-called nucleophilic pathway, which is not viable in proteolytic reactions, leads to a stable acyl-enzyme complex. However, the nucleophilic pathway is nonproductive as it is blocked by a high barrier in the deacylation step. On the basis of results reported here and in our earlier publication, a unified model is proposed to account for nearly all experimental observations concerning the catalysis of CPA.

AB - The catalytic mechanism of carboxypeptidase A (CPA) for the hydrolysis of ester substrates is investigated using hybrid quantum mechanical/molecular mechanical (QM/MM) methods and high-level density functional theory. The prevailing mechanism was found to utilize an active-site water molecule assisted by Glu270, and this so-called promoted-water pathway is similar to that in the CPA catalyzed proteolytic reaction (D. Xu and H. Guo, J. Am. Chem. Soc. 2009, 131, 9780). On the other hand, our simulations indicated the existence of an alternative pathway due to direct nucleophilic attack of Glu270 on the scissile carbonyl carbon. This so-called nucleophilic pathway, which is not viable in proteolytic reactions, leads to a stable acyl-enzyme complex. However, the nucleophilic pathway is nonproductive as it is blocked by a high barrier in the deacylation step. On the basis of results reported here and in our earlier publication, a unified model is proposed to account for nearly all experimental observations concerning the catalysis of CPA.

KW - Biocatalysis

KW - Carboxypeptidases A

KW - Catalytic Domain

KW - Hydrolysis

KW - Quantum Theory

KW - Thermodynamics

KW - Water

U2 - 10.1021/jp101448j

DO - 10.1021/jp101448j

M3 - Journal article

C2 - 20583802

VL - 114

SP - 9259

EP - 9267

JO - Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical

JF - Journal of Physical Chemistry Part B: Condensed Matter, Materials, Surfaces, Interfaces & Biophysical

SN - 1520-6106

IS - 28

ER -

ID: 94571420