Theoretical study of the mechanism of carboxypeptidase a inhibition by zinc ions

Silvia Alvarez-Santos; Angels González-Lafont; José M. Lluch; Baldomero Oliva; Francesc X. Avilés

Theoretical study of the mechanism of carboxypeptidase a inhibition by zinc ions

Silvia Alvarez-Santos, Angels González-Lafont, José M. Lluch, Baldomero Oliva, Francesc X. Avilés

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Abstract

The zinc inhibition mechanism of carboxypeptidase A (CPA) has been theoretically studied by both semiempirical quantum mechanical and Molecular Dynamics calculations. Zinc monohydroxide, zinc dihydroxide and zinc trihydroxide, solvated by two, one or zero water molecules, respectively, have been chosen as potential inhibitors. The inhibition mechanism takes place through the formation of a stabilizing hydroxide bridge between the inhibitory zinc ion of zinc monohydroxide and the catalytic zinc ion. This kind of structure has already been proposed by Larsen and Auld13from their experimental results. Once the bridge is formed within the CPA-zinc monohydroxide complex, the system is unable to evolve towards cleavage of the substrate peptide bond. © CNRS-Gauthier-Villars.

Original language	English
Pages (from-to)	979-984
Journal	New Journal of Chemistry
Volume	20
Issue number	9
Publication status	Published - 1 Dec 1996

Cite this

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title = "Theoretical study of the mechanism of carboxypeptidase a inhibition by zinc ions",

abstract = "The zinc inhibition mechanism of carboxypeptidase A (CPA) has been theoretically studied by both semiempirical quantum mechanical and Molecular Dynamics calculations. Zinc monohydroxide, zinc dihydroxide and zinc trihydroxide, solvated by two, one or zero water molecules, respectively, have been chosen as potential inhibitors. The inhibition mechanism takes place through the formation of a stabilizing hydroxide bridge between the inhibitory zinc ion of zinc monohydroxide and the catalytic zinc ion. This kind of structure has already been proposed by Larsen and Auld13from their experimental results. Once the bridge is formed within the CPA-zinc monohydroxide complex, the system is unable to evolve towards cleavage of the substrate peptide bond. {\textcopyright} CNRS-Gauthier-Villars.",

author = "Silvia Alvarez-Santos and Angels Gonz{\'a}lez-Lafont and Lluch, {Jos{\'e} M.} and Baldomero Oliva and Avil{\'e}s, {Francesc X.}",

year = "1996",

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language = "English",

volume = "20",

pages = "979--984",

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TY - JOUR

T1 - Theoretical study of the mechanism of carboxypeptidase a inhibition by zinc ions

AU - Alvarez-Santos, Silvia

AU - González-Lafont, Angels

AU - Lluch, José M.

AU - Oliva, Baldomero

AU - Avilés, Francesc X.

PY - 1996/12/1

Y1 - 1996/12/1

N2 - The zinc inhibition mechanism of carboxypeptidase A (CPA) has been theoretically studied by both semiempirical quantum mechanical and Molecular Dynamics calculations. Zinc monohydroxide, zinc dihydroxide and zinc trihydroxide, solvated by two, one or zero water molecules, respectively, have been chosen as potential inhibitors. The inhibition mechanism takes place through the formation of a stabilizing hydroxide bridge between the inhibitory zinc ion of zinc monohydroxide and the catalytic zinc ion. This kind of structure has already been proposed by Larsen and Auld13from their experimental results. Once the bridge is formed within the CPA-zinc monohydroxide complex, the system is unable to evolve towards cleavage of the substrate peptide bond. © CNRS-Gauthier-Villars.

AB - The zinc inhibition mechanism of carboxypeptidase A (CPA) has been theoretically studied by both semiempirical quantum mechanical and Molecular Dynamics calculations. Zinc monohydroxide, zinc dihydroxide and zinc trihydroxide, solvated by two, one or zero water molecules, respectively, have been chosen as potential inhibitors. The inhibition mechanism takes place through the formation of a stabilizing hydroxide bridge between the inhibitory zinc ion of zinc monohydroxide and the catalytic zinc ion. This kind of structure has already been proposed by Larsen and Auld13from their experimental results. Once the bridge is formed within the CPA-zinc monohydroxide complex, the system is unable to evolve towards cleavage of the substrate peptide bond. © CNRS-Gauthier-Villars.

M3 - Article

VL - 20

SP - 979

EP - 984

IS - 9

ER -

Theoretical study of the mechanism of carboxypeptidase a inhibition by zinc ions

Abstract

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