How calcium inhibits the magnesium‐dependent enzyme human phosphoserine phosphatase

Peeraer, Yves; Rabijns, A.; Collet, Jean-François; Schaftingen, Emile Van; Ranter, Camiel De

doi:10.1111/j.0014-2956.2004.04277.x

Cited by 50 publications

(44 citation statements)

References 28 publications

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“…It is possible that the coordination of Ca 2ϩ became more favored as compared with Mg 2ϩ (especially at the lower temperature) in the mutated catalytic site and inhibited the phosphorylation. In phosphoserine phosphatase, a member of the haloacid dehalogenase superfamily of SERCAs, the coordination geometry of Ca 2ϩ at the catalytic site was previously revealed to be different from that of the native cofactor Mg 2ϩ and therefore not suitable for catalysis (46 (38,39) was recently interpreted as a transient conformation for phosphoryl transfer (48). Consistently, the rate-limiting step for EP formation from E1Ca 2 and MgATP was previously shown to be the conformational change in the E1Ca 2 ⅐MgATP complex (to bring ␥-phosphate to Asp 351 (50)) preceding the phosphoryl transfer (50 -52).…”

Section: Summary Of Defects In 51 Dd Mutants-we Have Examinedmentioning

confidence: 99%

Comprehensive Analysis of Expression and Function of 51 Sarco(endo)plasmic Reticulum Ca2+-ATPase Mutants Associated with Darier Disease

Miyauchi

Daiho

Yamasaki

et al. 2006

Journal of Biological Chemistry

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We examined possible defects of sarco(endo)plasmic reticulum Ca catalyze Ca 2ϩ transport coupled with ATP hydrolysis (Fig. 1) and play an essential role in maintaining Ca 2ϩ homeostasis in the cytoplasm and endoplasmic reticulum lumen of cells (1-7). SERCAs have three cytoplasmic domains: phosphorylation (P), nucleotide binding (N), and actuator (A) and 10 transmembrane helices (M1-M10 or 11 in the SERCA2b isoform, M11). In the Ca 2ϩ transport cycle, the ATPase is activated by the binding of two Ca 2ϩ ions from the cytoplasm to the transport sites composed of M4, M5, M6, and M8 (E2 3 E1Ca 2 , step 1). Asp 351 in the P domain is then phosphorylated with MgATP to form the phosphorylated intermediate (EP) (step 2). During dephosphorylation of EP, the Ca 2ϩ ions are released into the lumen. In the detailed mechanism, the dephosphorylation process includes the conformational transition of EP associated with Ca 2ϩ release (step 3) and the subsequent hydrolysis of the acylphosphate bond (step 4).The three human SERCA genes encode SERCA isoforms (8 -10). Mutations in the SERCA2 gene (ATP2A2) and the resulting defects in the SERCA2b housekeeping isoform cause an autosomal dominant genetic skin disease, Darier disease (DD) (11,12). Over 100 mutations have been found with the DD pedigrees (11-24). They include many nonsense mutations, and also substitution and deletion mutations of amino acid residues. The mutations are located throughout the SERCA2b molecule and show no "hot spots" on the primary sequence. To understand how each of the substitution and deletion mutations affects SERCA2b protein, a limited number of mutations had been explored (9 by Ahn et al. (25), 10 by Dode et al. (23), 3 by Sato et al. (26) (a total of 20 because of overlap in Refs. 23 and 25)). To provide a comprehensive insight into the molecular basis of DD, as well as to understand the basis for each case of the DD pedigrees, it is necessary to analyze further the many unexplored substitution and deletion mutations. We therefore carried out in this study a comprehensive analysis of the expression and function of most of the DD causing substitution and deletion mutations reported, i.e. the 51 mutations shown in Fig. 2. Our results showed that most of the mutations (48 of the 51) cause severe defects in protein expression and/or Ca 2ϩ transport function. The loss of the transport function was ascribed to markedly reduced ATP hydrolysis or uncoupling from ATP hydrolysis. The remaining three mutations were exceptional in that they exhibited seemingly normal protein expression and

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Section: Summary Of Defects In 51 Dd Mutants-we Have Examinedmentioning

confidence: 99%

Comprehensive Analysis of Expression and Function of 51 Sarco(endo)plasmic Reticulum Ca2+-ATPase Mutants Associated with Darier Disease

Miyauchi

Daiho

Yamasaki

et al. 2006

Journal of Biological Chemistry

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“…In fact, Ca 2ϩ itself appears to be able to bind to the corresponding catalytic site in phosphoserine phosphatase, though with an altered coordinate geometry (seven instead of six coordinates), if the crystallization buffer contains 0.7 M Ca 2ϩ (36). Thus, the identity of the metal bound to the catalytic site in the crystalline E1⅐AMPPCP complex of ATPase might be worth re-examining, even though coordinate geometries, distances, and B factors in the E1⅐AMPPCP crystalline form initially suggested that this metal was mostly Mg 2ϩ (4,5 (together with destabilization of that particular conformation of nucleotide), as in fact found in the E1⅐AMPPCP crystals, which have only one Mg 2ϩ ion bound, instead of two in the E1⅐ADP⅐AlFx or E2⅐MgF 4 ⅐ADP crystals (4 -6) (see Supplemental Material for additional discussion).…”

Section: Amppcp Versus Adp⅐alfx and Ca 2ϩ Ion Occlusion In Serca1amentioning

confidence: 99%

The Average Conformation at Micromolar [Ca2+] of Ca2+-ATPase with Bound Nucleotide Differs from That Adopted with the Transition State Analog ADP·AlFx or with AMPPCP under Crystallization Conditions at Millimolar [Ca2+]

Picard

Toyoshima²,

Champeil³

2005

Journal of Biological Chemistry

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Crystalline forms of detergent-solubilized sarcoplasmic reticulum Ca 2؉ -ATPase, obtained in the presence of either a substrate analog, AMPPCP, or a transition state complex, ADP⅐fluoroaluminate, were recently described to share the same general architecture despite the fact that, when studied in a test tube, these forms show different functional properties. Here, we show that the differences in the properties of the E1⅐AMPPCP and the E1⅐ADP⅐AlFx membraneous (or solubilized) forms are much less pronounced when these properties are examined in the presence of 10 mM Ca 2؉ (the concentration prevailing in the crystallization media) than when they are examined in the presence of the few micromolar of Ca 2؉ known to be sufficient to saturate the transport sites. This concerns various properties, including ATPase susceptibility to proteolytic cleavage by proteinase K, ATPase reactivity toward SH-directed Ellman's reagent, ATPase intrinsic fluorescence properties (here described for the E1⅐ADP⅐AlFx complex for the first time), and also the rates of 45 Ca 2؉ -40 Ca 2؉ exchange at site "II." These results solve the above paradox at least partially and suggest that the presence of a previously unrecognized Ca 2؉ ion in the E1⅐AMPPCP crystals should be re-investigated. A contrario, they emphasize the fact that the average conformation of the E1⅐AMPPCP complex under usual conditions in the test tube differs from that found in the crystalline form. The extended conformation of nucleotide revealed by the E1⅐AMPPCP crystalline form might be only indicative of the requirements for further processing of the complex, toward the transition state leading to phosphorylation and Ca 2؉ occlusion.

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“…Compounds containing Ca 2+ ions have an inhibiting effect on phosphatases (Mamedov et al, 2001;Peeraer et al, 2004).…”

Section: Resultsmentioning

confidence: 99%

Kinetic characterization and molecular modeling of trehalose-6-phosphate phosphatase from Anopheles gambiae and expressed in Pichia pastoris

Pessoa¹,

Izumi²,

Zanotto³

et al. 2017

Afr. J. Biotechnol.

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Trehalose-6-phosphate phosphatase (TPP) is one of the primary enzymes involved in the synthesis of trehalose, the main sugar found in insect hemolymph. In the present study, we report for the first time heterologous expression in Pichia pastoris, characterization and homology modeling of TPP from Anopheles gambiae mosquito. Purified TPP recombinant exhibited a molecular weight of approximately 36 kDa with optimum pH of 8.0, optimum temperature of 38°C, and the K M was 3.19 ± 0.10 mM. Inhibition tests revealed that CaCl 2 and Ca(NO 3 ) 2 at 5 and 25 mM, respectively, were effective inhibitors of TPP activity. Homology studies and molecular modeling indicated high similarity of the TPP tridimensional structure with TPP enzymes deposited at a data bank and these homology studies confirmed that it is a trehalose phosphatase with conserved motifs of the superfamily haloacid dehydrogenase. These results may provide support for the discovering of TPP inhibitors to be used for development of insecticides to control mosquito vectors.

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How calcium inhibits the magnesium‐dependent enzyme human phosphoserine phosphatase

Cited by 50 publications

References 28 publications

Comprehensive Analysis of Expression and Function of 51 Sarco(endo)plasmic Reticulum Ca2+-ATPase Mutants Associated with Darier Disease

Comprehensive Analysis of Expression and Function of 51 Sarco(endo)plasmic Reticulum Ca2+-ATPase Mutants Associated with Darier Disease

The Average Conformation at Micromolar [Ca2+] of Ca2+-ATPase with Bound Nucleotide Differs from That Adopted with the Transition State Analog ADP·AlFx or with AMPPCP under Crystallization Conditions at Millimolar [Ca2+]

Kinetic characterization and molecular modeling of trehalose-6-phosphate phosphatase from Anopheles gambiae and expressed in Pichia pastoris

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