Showing papers on "Purple acid phosphatases published in 2009"
TL;DR: In this paper, a microreview describes the structures and properties of a number of bimetallic complexes designed as both structural and functional mimics of the active sites of some specific metallohydrolase enzymes.
Abstract: This microreview describes the structures and properties of a number of bimetallic complexes designed as both structural and functional mimics of the active sites of some specific metallohydrolase enzymes. The metalloenzymes in question include the predominantly monoesterase-activity-displaying purple acid phosphatase (PAP) and di- and triesterase enzymes, which have significant roles in the bioremedial hydrolysis of organophosphate pesticides and nerve gases. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
100 citations
TL;DR: The localization of the tartrate‐resistant purple acid phosphatase in osteoclasts is consistent with an intracellular function for this enzyme, and no consistent extracellular activity could be detected, nor was any reaction product observed at the ruffed border.
Abstract: The intracellular localization of the tartrate-resistant purple acid phosphatase in osteoclasts of developing rat bone has been determined immunocytochemically using an antiserum to the purified bone-derived purple acid phosphatase. The localization of the immunoreactivity was compared with the results of enzyme histochemistry using p-nitrophenylphosphate as substrate and 10 mM tartrate. Both methods revealed the presence of the enzyme in numerous vesicles of various sizes up to 2–3 μm in diameter and in granules. There was no immunoreactivity in the Golgi apparatus, and tartrate completely inhibited the histochemical activity of this organelle. No consistent extracellular activity could be detected, nor was any reaction product observed at the ruffled border. The localization of the tartrate-resistant purple acid phosphatase in osteoclasts is consistent with an intracellular function for this enzyme.
73 citations
TL;DR: The Mn(II)-Mn(II) system models these distant relatives of PAPs that may have evolved from distantly related divalent dinuclear metallohydrolases that operate under pH neutral conditions by stabilization of a trivalent-divalent metal-ion core.
Abstract: The currently accepted paradigm is that the purple acid phosphatases (PAPs) require a heterovalent, dinuclear metal-ion center for catalysis It is believed that this is an essential feature for these enzymes in order for them to operate under acidic conditions A PAP from sweet potato is unusual in that it appears to have a specific requirement for manganese, forming a unique Fe(III)-mu-(O)-Mn(II) center under catalytically optimal conditions (Schenk et al Proc Natl Acad Sci USA 2005, 102, 273) Herein, we demonstrate, with detailed electron paramagnetic resonance (EPR) spectroscopic and kinetic studies, that in this enzyme the chromophoric Fe(III) can be replaced by Mn(II), forming a catalytically active, unprecedented antiferromagnetically coupled homodivalent Mn(II)-mu-(H)OH-mu-carboxylato-Mn(II) center in a PAP However, although the enzyme is still active, it no longer functions as an acid phosphatase, having optimal activity at neutral pH Thus, PAPs may have evolved from distantly related divalent dinuclear metallohydrolases that operate under pH neutral conditions by stabilization of a trivalent-divalent metal-ion core The present Mn(II)-Mn(II) system models these distant relatives, and the results herein make a significant contribution to our understanding of the role of the chromophoric metal ion as an activator of the nucleophile In addition, the detailed analysis of strain broadened EPR spectra from exchange-coupled dinuclear Mn(II)-Mn(II) centers described herein provides the basis for the full interpretation of the EPR spectra from other dinuclear Mn metalloenzymes
63 citations
TL;DR: Kinetic studies suggest a mechanism in which a terminal M(III)-bound hydroxide is the hydrolysis-initiating nucleophilic catalyst in the novel isostructural Fe(III)Co(II)(BPBPMP)Fe(III)(mu-OAc)(2)M(II) complexes, which show maximum catalytic activity in DNA Hydrolysis near physiological pH.
Abstract: The design and development of suitable biomimetic catalytic systems capable of mimicking the functional properties of enzymes continues to be a challenge for bioinorganic chemists. In this study, we report on the synthesis, X-ray structures, and physicochemical characterization of the novel isostructural [(FeCoII)-Co-III(BPBPMP)(mu-OAc)(2)]ClO4 (1) and [(GaCoII)-Co-III(BPBPMP)(mu-OAc)(2)]ClO4 (2) complexes with the unsymmetrical dinucleating ligand H2BPBPMP {2-bis[{(2-pyridyl-methyl)-aminomethyl)-6-{(2-hydroxy-benzyl)-(2-pyridyl-methyl)}-aminomethyl]-4-methylphenol). The previously reported complex [(FeZnII)-Zn-III(BPBPMP)(mu-OAc)(2)]ClO4 (3) was investigated here by electron paramagnetic resonance for comparison with such studies on 1 and 2. A magneto-structural correlation between the exchange parameter J (cm(-1)) and the average bond lengh d (angstrom) of the [Fe-III-O-M-II] structural unit for 1 and for related isostructural (FeMII)-M-III complexes using the correlation J = -10(7) exp(-6.8d) reveals that this parameter is the major factor that determines the degree of antiferromagnetic coupling in the series [(BPBPMP)Fe-III(mu-OAc)(2)M-II](+) (M-II = Mn, Fe, Co, Ni) of complexes. Potentiometric and spectrophotometric titrations along with electronic absorption studies show that, in aqueous solution, complexes 1 and 2 generate the [(HO)M-III(mu-OH)Co-II(H2O)] complex as the catalytically active species in diester hydrolysis reactions, Kinetic studies on the hydrolysis of the model substrate bis(2,4-dinitrophenyl)phosphate by 1 and 2 show Michaelis-Menten behavior, with 2 being 35% more active than 1. In combination with k(H)/k(D) isotope effects, the kinetic studies suggest a mechanism in which a terminal M-III-bound hydroxide is the hydrolysis-initiating nucleophilic catalyst. In addition, the complexes show maximum catalytic activity in DNA hydrolysis near physiological pH. The modest reactivity difference between 1 and 2 is consistent with the slightly increased nucleophilic character of the Ga-III-OH terminal group in comparison to Fe-III-OH in the dinuclear (MCoII)-Co-III species.
56 citations
TL;DR: The design and synthesis of derivatives of 1-naphthylmethylphosphonic acids as inhibitors of PAP are described, with K(i) values as low as 4 microM, the lowest reported to date for a PAP inhibitor.
36 citations
TL;DR: The findings suggest that not all members in the PAP family have acidic pH optimum and broad substrate specificity.
25 citations
TL;DR: Electronic structure calculations using density functional theory have confirmed the conclusions derived from the experimental investigations of the Mn(II)Mn(III) system and mechanisms are discussed.
Abstract: The binuclear heterovalent manganese model complex [Mn(II)Mn(III)(L1)(OAc)(2)] ClO(4) x H(2)O (H(2)L1 = 2-(((3-((bis(pyridin-2-ylmethyl)amino)methyl)-2-hydroxy-5-methylbenzyl)(pyridin-2-ylmethyl)amino)-methyl)phenol) has been prepared and studied structurally, spectroscopically, and computationally. The magnetic and electronic properties of the complex have been related to its structure. The complex is weakly antiferromagnetically coupled (J approximately -5 cm(-1), H = -2J S(1) x S(2)) and the electron paramagnetic resonance (EPR) and magnetic circular dichroism (MCD) spectra identify the Jahn-Teller distortion of the Mn(III) center as predominantly a tetragonal compression, with a significant rhombic component. Electronic structure calculations using density functional theory have confirmed the conclusions derived from the experimental investigations. In contrast to isostructural M(II)Fe(III) complexes (M = Fe, Mn, Zn, Ni), the Mn(II)Mn(III) system is bifunctional possessing both catalase and hydrolase activities, and only one catalytically relevant pK(a) (= 8.2) is detected. Mechanistic implications are discussed.
22 citations
TL;DR: Despite low amino‐acid sequence homology of PPD1 to well‐characterized ∼55‐kDa purple acid phosphatases, their overall fold, topology of active center and metal content are highly similar.
14 citations
TL;DR: The electronic structure and magnetic interactions of the active site of sweet potato purple acid phosphatase (PAP) were investigated by using UHF, pure DFT, and hybrid DFT methods, indicating that this stronger antiferromagnetic coupling is caused by a mu-oxo bridge in the Fe(III)-Mn(II) binuclear metal center.
Abstract: The electronic structure and magnetic interactions of the active site of sweet potato purple acid phosphatase (PAP) were investigated by using UHF, pure DFT (UBLYP), and hybrid DFT methods (UB3LYP and UB2LYP). PAP catalyzes the hydrolysis of a phosphate ester under acidic conditions and contains a binuclear metal center. Sweet potato PAP provides stronger antiferromagnetic coupling than other PAPs. UB3LYP showed reasonably good agreement with the experimental magnetic coupling, indicating that this stronger antiferromagnetic coupling is caused by a µ-oxo bridge in the Fe(III)-Mn(II) binuclear metal center, which is the origin of the asymmetric spin delocalization. The type of bridging ligand is essential for the reaction mechanism, because the bridging ligand is suggested to function as a nucleophile in the reaction. Analyses of the natural orbital and spin density distributions implied the asymmetric spin delocalization on the bridging oxygen. The mechanism and the pathway of the antiferromagnetic coupling between Fe(III) and Mn(II) were discussed, using chemical indices introduced with the occupation numbers of singly occupied natural orbitals.
6 citations
TL;DR: In this article, a microreview describes the structures and properties of a number of bimetallic complexes designed as both structural and functional mimics of the active sites of some specific metallohydrolase enzymes.
Abstract: This microreview describes the structures and properties of a number of bimetallic complexes designed as both structural and functional mimics of the active sites of some specific metallohydrolase enzymes. The metalloenzymes in question include the predominantly monoesterase-activity-displaying purple acid phosphatase (PAP) and di- and triesterase enzymes, which have significant roles in the bioremedial hydrolysis of organophosphate pesticides and nerve gases. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)