A structural and catalytic model for zinc phosphoesterases

Rebecca R. Buchholz; Morgan E. Etienne; Anneke Dorgelo; Ruth E. Mirams; Sarah J. Smith; Shiao Yun Chow; Lyall R. Hanton; Geoffrey B. Jameson; Gerhard Schenk; Lawrence R. Gahan

doi:10.1039/b806391e

A structural and catalytic model for zinc phosphoesterases

Rebecca R. Buchholz
, Morgan E. Etienne
, Anneke Dorgelo
, Ruth E. Mirams
, Sarah J. Smith
, Shiao Yun Chow
, Lyall R. Hanton
, Geoffrey B. Jameson
, Gerhard Schenk
, Lawrence R. Gahan

Atmospheric Composition Remote Sensing and Prediction

Research output: Contribution to journal › Article › peer-review

26 Scopus citations

Abstract

A structural model for the active site of phosphoesterases, enzymes that degrade organophosphate neurotoxins, has been synthesised. The ligand [2-((2-hydroxy-3-(((2-hydroxyethyl)(pyridin-2-ylmethyl)amino)methyl) -5-methylbenzyl)(pyridin-2-ylmethyl)amino)acetic acid] (H₃L1) and two Zn(ii) complexes have been prepared and characterised as [Zn ₂(HL1)(CH₃COO)](PF₆)·H₂O and Li[Zn₂(HL1)]₄(PO₄)₂(PF ₆)₃·(CH₃OH). The ligand (H ₃L1) and complex [Zn₂(HL1)(CH₃COO)](PF ₆)·H₂O were characterised through ¹H NMR, ¹³C NMR, mass spectroscopy and microanalysis. The X-ray crystal structure of Li[Zn₂(HL1)]₄(PO₄) ₂(PF₆)₃·(CH₃OH) revealed a tetramer of dinuclear complexes, bridged by two phosphate molecules and bifurcating acetic acid arms. Functional studies of the zinc complex with the substrate bis(4-nitrophenyl)phosphate (bNPP) determined the complex with HL1^2- to be a competent catalyst with k_cat = 1.26 ± 0.06 × 10^-6 s^-1.

Original language	English
Pages (from-to)	6045-6054
Number of pages	10
Journal	Dalton Transactions
Issue number	43
DOIs	https://doi.org/10.1039/b806391e
State	Published - 2008

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@article{368d52692f934cc4ba7440838f84fe8d,

title = "A structural and catalytic model for zinc phosphoesterases",

abstract = "A structural model for the active site of phosphoesterases, enzymes that degrade organophosphate neurotoxins, has been synthesised. The ligand [2-((2-hydroxy-3-(((2-hydroxyethyl)(pyridin-2-ylmethyl)amino)methyl) -5-methylbenzyl)(pyridin-2-ylmethyl)amino)acetic acid] (H3L1) and two Zn(ii) complexes have been prepared and characterised as [Zn 2(HL1)(CH3COO)](PF6)·H2O and Li[Zn2(HL1)]4(PO4)2(PF 6)3·(CH3OH). The ligand (H 3L1) and complex [Zn2(HL1)(CH3COO)](PF 6)·H2O were characterised through 1H NMR, 13C NMR, mass spectroscopy and microanalysis. The X-ray crystal structure of Li[Zn2(HL1)]4(PO4) 2(PF6)3·(CH3OH) revealed a tetramer of dinuclear complexes, bridged by two phosphate molecules and bifurcating acetic acid arms. Functional studies of the zinc complex with the substrate bis(4-nitrophenyl)phosphate (bNPP) determined the complex with HL12- to be a competent catalyst with kcat = 1.26 ± 0.06 × 10-6 s-1.",

author = "Buchholz, \{Rebecca R.\} and Etienne, \{Morgan E.\} and Anneke Dorgelo and Mirams, \{Ruth E.\} and Smith, \{Sarah J.\} and Chow, \{Shiao Yun\} and Hanton, \{Lyall R.\} and Jameson, \{Geoffrey B.\} and Gerhard Schenk and Gahan, \{Lawrence R.\}",

year = "2008",

doi = "10.1039/b806391e",

language = "English",

pages = "6045--6054",

journal = "Dalton Transactions",

issn = "1477-9226",

publisher = "Royal Society of Chemistry",

number = "43",

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T1 - A structural and catalytic model for zinc phosphoesterases

AU - Buchholz, Rebecca R.

AU - Etienne, Morgan E.

AU - Dorgelo, Anneke

AU - Mirams, Ruth E.

AU - Smith, Sarah J.

AU - Chow, Shiao Yun

AU - Hanton, Lyall R.

AU - Jameson, Geoffrey B.

AU - Schenk, Gerhard

AU - Gahan, Lawrence R.

PY - 2008

Y1 - 2008

N2 - A structural model for the active site of phosphoesterases, enzymes that degrade organophosphate neurotoxins, has been synthesised. The ligand [2-((2-hydroxy-3-(((2-hydroxyethyl)(pyridin-2-ylmethyl)amino)methyl) -5-methylbenzyl)(pyridin-2-ylmethyl)amino)acetic acid] (H3L1) and two Zn(ii) complexes have been prepared and characterised as [Zn 2(HL1)(CH3COO)](PF6)·H2O and Li[Zn2(HL1)]4(PO4)2(PF 6)3·(CH3OH). The ligand (H 3L1) and complex [Zn2(HL1)(CH3COO)](PF 6)·H2O were characterised through 1H NMR, 13C NMR, mass spectroscopy and microanalysis. The X-ray crystal structure of Li[Zn2(HL1)]4(PO4) 2(PF6)3·(CH3OH) revealed a tetramer of dinuclear complexes, bridged by two phosphate molecules and bifurcating acetic acid arms. Functional studies of the zinc complex with the substrate bis(4-nitrophenyl)phosphate (bNPP) determined the complex with HL12- to be a competent catalyst with kcat = 1.26 ± 0.06 × 10-6 s-1.

AB - A structural model for the active site of phosphoesterases, enzymes that degrade organophosphate neurotoxins, has been synthesised. The ligand [2-((2-hydroxy-3-(((2-hydroxyethyl)(pyridin-2-ylmethyl)amino)methyl) -5-methylbenzyl)(pyridin-2-ylmethyl)amino)acetic acid] (H3L1) and two Zn(ii) complexes have been prepared and characterised as [Zn 2(HL1)(CH3COO)](PF6)·H2O and Li[Zn2(HL1)]4(PO4)2(PF 6)3·(CH3OH). The ligand (H 3L1) and complex [Zn2(HL1)(CH3COO)](PF 6)·H2O were characterised through 1H NMR, 13C NMR, mass spectroscopy and microanalysis. The X-ray crystal structure of Li[Zn2(HL1)]4(PO4) 2(PF6)3·(CH3OH) revealed a tetramer of dinuclear complexes, bridged by two phosphate molecules and bifurcating acetic acid arms. Functional studies of the zinc complex with the substrate bis(4-nitrophenyl)phosphate (bNPP) determined the complex with HL12- to be a competent catalyst with kcat = 1.26 ± 0.06 × 10-6 s-1.

UR - https://www.scopus.com/pages/publications/55149118943

U2 - 10.1039/b806391e

DO - 10.1039/b806391e

M3 - Article

C2 - 19082062

AN - SCOPUS:55149118943

SN - 1477-9226

SP - 6045

EP - 6054

JO - Dalton Transactions

JF - Dalton Transactions

IS - 43

ER -

A structural and catalytic model for zinc phosphoesterases

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