Intestinal alkaline phosphatase. Catalytic properties and half of the sites reactivity

Chappelet-Tordo, Danielle; Fosset, Michel; Iwatsubo, Motohiro; Gache, Christian; Lazdunski, Michel

doi:10.1021/bi00706a002

Cited by 136 publications

(65 citation statements)

References 36 publications

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“…Duplicate experiments using VOSO 4 and Na 3 VO 4 were run under identical conditions. Calf-intestine APase has been reported to be a halfsite enzyme that follows Michaelis-Menten kinetics [5]. In this investigation, the results obtained demonstrated a small negative cooperativity.…”

Section: Methodsmentioning

confidence: 48%

“…Calfintestine APase is one of the most thoroughly studied phosphatases among the mammalian APases. Numerous methods have been employed in its characterization [5][6][7][8] , and selected amino acids [9][10][11]. Vanadium compounds are known phosphatase inhibitors, for example, sodium orthovanadate is a competitive inhibitor for E. coli APase with a K i of 12 mM [12].…”

Section: Introductionmentioning

confidence: 99%

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Alkaline phosphatase inhibition by vanadyl-β-diketone complexes: electron density effects

Ziegler

Florián

Ballícora

et al. 2008

Journal of Enzyme Inhibition and Medicinal Chemistry

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A series of systematically modified vanadyl-b-diketone complexes, VO(b-diketone) 2 , bearing substituent groups with different electron inductive properties were synthesized and evaluated as inhibitors against calf-intestine alkaline phosphatase (APase). A combination of biochemical and quantum mechanical techniques were employed to identify structure-activity relationships relevant for rational design of phosphatase inhibitors. Kinetic parameters and activation free energy, enthalpy, and entropy for calf-intestine APase-catalyzed dephosphorylation of para-nitrophenylphosphate were also determined along with the inhibition constants (K i ) for the VO(b-diketone) 2 complexes. Increased positive charge on the vanadyl group increases the inhibition potency of the complex while the absence of an available coordination site on the complex decreases its inhibition potency. These findings correlate well with the results of ab initio electron density calculations for the complexes.

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Section: Methodsmentioning

confidence: 48%

Section: Introductionmentioning

confidence: 99%

Alkaline phosphatase inhibition by vanadyl-β-diketone complexes: electron density effects

Ziegler

Florián

Ballícora

et al. 2008

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Unmodified BIALP without free PEG showed profiles with an optimal pH of 8.5-9.5, which agreed well with previous reports. [25][26][27] Unmodified BIALP plus 5% PEG2000 and pegylated BIALP showed the same profiles. The v 0 values at pH 9.0 of unmodified BIALP plus 5% PEG2000 and pegylated BIALP were 86 AE 2 and 83 AE 3 nM/s respectively, higher than of that of unmodified BIALP without free PEG (64 AE 2 nM/s).…”

Section: Pegylation Of Bialpmentioning

confidence: 74%

Effects of Polyethylene Glycol on Bovine Intestine Alkaline Phosphatase Activity and Stability

Sekiguchi

Yasukawa

Inouye

2011

Bioscience, Biotechnology, and Biochemistry

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“…The mutation alters the rate constant for the conformational change that controls the phosphorylation at alkaline pH from k, > 1000 s-' for the wild-type enzyme [24] to k2 = 10 s-' for the U-47 activated enzyme [3]. The rate of dephosphorylation of the mono-phospho derivative, k,, is decreased only by a factor of 4.…”

Section: Discussionmentioning

confidence: 99%

Effects of Antibodies to Various MÒlecular Forms of a Mutationally Altered Escherichia coli Alkaline Phosphatase on Its Activation by Zinc

Pagès¹,

Lazdunski²

1976

European Journal of Biochemistry

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Immunogenic and antigenic properties of a Zn2 +-deficient alkaline phosphatase produced in a mutant (U-47) of E.sclierichia coli have been studied. The native U-47 enzyme, that exists in a monomerdimer equilibrium, was used as immunogen. From the antisera obtained, four antibody populations directed to the various molecular forms of U-47 enzyme have been purified by affinity chromatography using specific antigens coupled to glutaraldehyde-activated beads of indubiose. 70 '!;) of the total antibody obtained was directed both to the monomeric and the dirneric forms, 9% wils directed to the dimer but showed a low affinity for the monomer; 10% and 11% were specifically directed respectively to the monomer-and the dimer. Each antibody population purified had a specific effect on the catalytic activity of the Zn2+-activated U-47 enzyme. The anti-monomer-dimer and the anti-dimer-monomer inhibit to the same extent whereas the specific anti-monomer does not alter the activity significantly and the specific anti-dimer causes a 30% activation. The catalytic activity of the alkaline phosphatase produced in wild-type strains was also reduced by thesc anti-U-47 enzyme antibodies. However, whereas the anti-monomer had again very little effect, the anti-dimermonomer and the anti-monomer-dimer inhibited this enzyme to different extents. The specific antidimer also inhibited this wild-type alkaline phosphate. Antibodies of high affinity to the dimeric form of U-47 enzyme, i. e. specific anti-dimer or anti-dimer-monomer, caused a 30"/;; activation when they were added prior to the reactivation process by ZnZ+. Specific anti-monomer strongly inhibited this reactivation process. The Fab fragment of the anti-wild-type phosphatase antibody, under the same conditions, caused a 300",, activation. The extents of interactions o f the various molecular forms of U-47 enzyme and of the wild-type enzyme with the anti-monomerdimer and with the anti-dimer have been determined. U-47 enzyme monomeric form has three determinants exposed and the dimeric form has five determinants exposed for interacting with the antimonomer-dimer antibody, the free wild-type enzyme has only two determinants exposed to this antibody. These determinants might be close to the active site or in another critical location since this antibody can reduce the catalytic activity of the wild-type enzyme to half the original value. The anti-dimer antibodies can interact with three determinants exposed at the surface of the free Zn2'-reactivated U-47 enzyme and the non-covalent binding of one mole of inorganic phosphate results in the exposure of one more antigenic determinant.

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Intestinal alkaline phosphatase. Catalytic properties and half of the sites reactivity

Cited by 136 publications

References 36 publications

Alkaline phosphatase inhibition by vanadyl-β-diketone complexes: electron density effects

Alkaline phosphatase inhibition by vanadyl-β-diketone complexes: electron density effects

Effects of Polyethylene Glycol on Bovine Intestine Alkaline Phosphatase Activity and Stability

Effects of Antibodies to Various MÒlecular Forms of a Mutationally Altered Escherichia coli Alkaline Phosphatase on Its Activation by Zinc

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