Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P06889 (Mol)
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We report here the complete determination of the solution structure of acylphosphatase, a small enzyme that catalyses the hydrolysis of organic acylphosphates, as determined by distance geometry methods based on nuclear magnetic resonance information. A non-standard strategy for the distance geometry calculations was used and is described here some detail. The five best structures were then refined by restrained energy minimization and molecular dynamics in order to explore the conformational space consistent with the experimental data. We address the question of whether the solution structure of acylphosphatase follows the general principles of protein structure, i.e. those learned from analysing crystal structures. Static and dynamic features are discussed in detail. An uncommon beta-alpha-beta motif, so far found only in procarboxypeptidase B and in an RNA-binding protein, is present in acylphosphatase.
J Mol Biol 1992 Mar 20
PMID:Three-dimensional structure of acylphosphatase. Refinement and structure analysis. 131 85

It has been proposed that combination of intraresidue, sequential and longer range nuclear Overhauser enhancements occurring in 1H nuclear magnetic resonance spectra of protein chains folded in a helix show a regular characteristic pattern. As a test case the spectra of horse muscle acylphosphatase were searched for this pattern together with other typical signs of a helical conformation (i.e. chemical shift, coupling constants and slow 2H-H exchange). Two amino acid sequences complying with these requirements were found. Just a few amino acid spin system assignments were then sufficient to locate the two segments within the primary structure (residues 22 to 35 and 55 to 66), thus providing the sequential assignment. The assignment of the side-chains was completed and a list of all nuclear magnetic resonance constraints within the two segments (126 intra- and 180 interresidue distances, 21 torsion angles phi and 19 hydrogen bonds) was produced. Distance geometry calculation shows that each segment forms an alpha-helix. The mutual orientation of the two helices was established subsequently.
J Mol Biol 1989 Jan 05
PMID:Identification and description of alpha-helical regions in horse muscle acylphosphatase by 1H nuclear magnetic resonance spectroscopy. 253 23

Nuclear magnetic resonance spectra of acylphosphatase were searched for signs of beta-structure, i.e. characteristic nuclear Overhauser enhancement patterns displayed in the two-dimensional spectra, typical chemical shifts, coupling constants and slow 2H-H exchange. The results provided identification of the main-chain resonances of amino acid residues involved in the beta-structure. The full sequential assignment of this region was gained by identification of some amino acid spin systems and their alignment with the primary sequence. The assignment of the side-chains was virtually completed subsequently and a list produced of nuclear magnetic resonance (n.m.r.) constraints derived from the spectra. The beta-structure consists of a beta-sheet with four antiparallel chains, one attached parallel chain, three tight turns and a beta-bulge. The conformation of the beta-sheet was determined by distance geometry calculation using the n.m.r. constraints (174 intraresidual, 107 sequential and 226 long-range distances, 32 torsion angles, phi, and 28 hydrogen bonds) as input. Observation of some interactions between the sheet and previously identified alpha-helical regions made it possible to give an outline of the three-dimensional structure of the enzyme.
J Mol Biol 1989 May 20
PMID:Identification and description of beta-structure in horse muscle acylphosphatase by nuclear magnetic resonance spectroscopy. 254 76

Sequence-specific assignment of 1H nuclear magnetic resonance spectra of acylphosphatase (EC 3.6.1.7) isolated from rabbit skeletal muscle have made it possible to identify short distance constraints from nuclear Overhauser enhancement spectra, to evaluate spin-spin coupling constants of many backbone amide hydrogens and to assess their slow exchange with deuterons in 2H2O solution. Analysis of these data show that the major regular secondary structure of the enzyme consists of five extended beta-strands, four of which are arranged in an antiparallel beta-sheet, while the fifth is attached parallel. A helix consisting of 11 residues has also been identified. Consideration of additional distance constraints between sequentially remote residues has allowed us to give an outline of the overall fold of the protein.
J Mol Biol 1988 Jan 05
PMID:Secondary structure of acylphosphatase from rabbit skeletal muscle. A nuclear magnetic resonance study. 283 9

Human skeletal muscle acylphosphatase, purified by a technique based on affinity chromatography on immunoadsorbent, has been sequenced completely using tryptic and peptic peptide series, prepared by reverse-phase high-pressure liquid chromatography. The sequence analysis was carried out on all the isolated tryptic peptides using a manual Edman degradation technique and time-course analysis of the released amino acids by carboxypeptidase A. The enzyme is NH2-blocked and the blocking group has been identified by fast atom bombardment mass spectrometry.
Mol Biol Med 1984 Dec
PMID:Human skeletal muscle acylphosphatase: the primary structure. 610 Jul 23

In vitro experiments demonstrated the ability of acylphosphatase to hydrolyze the phosphorylated intermediate that is formed during the activity of Na+, K(+)- and Ca(2+)-ATPases of mammalian cells membranes. In order to investigate the effect of this enzyme on intracellular cation levels, a synthetic gene for human muscle acylphosphatase has been expressed in E. coli strains BL21 and JM101. Intracellular total steady-state calcium concentration, as measured by isotopic exchange, was significantly higher in transformed cells as compared to controls and the rising was dependent on the level of acylphosphatase expression. Accordingly also free intracellular calcium concentration, as measured by Fura-2 fluorescence, increased in transformed cells. On the other hand, phosphate levels were not affected by the expression of acylphosphatase, while sodium and rubidium levels increase in transformed cells. Intracellular pH resulted to be slightly affected by the expression of acylphosphatase, cytoplasm of transformed JM101 bacteria being more alkaline (pH 7.45) as compared to control cells (pH 7.40). On the basis of these results, it can be suggested that acylphosphatase acts in vivo by regulating the cation transport in E. coli.
Biochem Mol Biol Int 1994 Aug
PMID:Expression of human acylphosphatase in Escherichia coli affects intracellular calcium levels. 784 13

The purpose of this study was to investigate whether vitamin D3 deficiency and 1,25-dihydroxyvitamin D3 treatment affect some aspects of heart metabolism in the rat. To this end, five experimental groups were studied: (1) the control group of the vitamin D3 supplemented rats (Group A); (2) rachitic rats (Group B); (3) rachitic rats treated with 1,25-dihydroxyvitamin D3 (Group C); (4) rats fed a vitamin D-deficient diet (Group D); (5) rats fed a vitamin D-deficient diet and treated with 1,25-dihydroxyvitamin D3 (Group E). The five groups were compared by checking in the heart some metabolic parameters, i.e. citrate content, and enzyme activities in cytosol and mitochondria. Citrate content was higher in the heart of treated animals when compared with the control. As regards the enzymatic activities in heart mitochondria, NAD(+)-dependent isocitrate dehydrogenase remarkably decreased in Group B rats and 1,25-dihydroxyvitamin D3 restored quite normal values. NADP(+)-dependent isocitrate dehydrogenase decreased in Group B and Group D animals, and 1,25-dihydroxyvitamin D3 treatment was effective in restoring control values. Cytochrome c oxidase activity did not change, while citrate synthase showed an increase in all the treated rats. As regards the cytosolic enzymes, fructose-6-phosphate kinase increased in the two groups of vitamin D-deplete rats in comparison with the control. Glyceraldehyde-3-phosphate dehydrogenase and 3-phosphoglycerate kinase showed a similar trend: an increase in all the treated animals. In heart homogenate, acylphosphatase and acid phosphatase activities were also determined. Acylphosphatase increased in the treated rats, while acid phosphatase decreased in the rats injected with 1,25-dihydroxyvitamin D3. These results support the hypothesis of a participation of 1,25-dihydroxyvitamin D3 in some aspects of heart metabolism.
J Mol Cell Cardiol 1994 Nov
PMID:Effect of vitamin D deficiency and 1,25-dihydroxyvitamin D3 on rat heart metabolism. 789 66

Acylphosphatase purified from heart muscle actively hydrolyzes the phosphoenzyme intermediate of cardiac sarcoplasmic reticulum Ca(2+)-ATPase. This effect was evident with acylphosphatase concentrations (up to 100 units/mg sarcoplasmic reticulum protein) that fall within the physiological range, and the low value of the apparent Km, on the order of 10(-7)M, suggests a high affinity towards this special substrate. Moreover, acylphosphatase addition to sarcoplasmic reticulum vesicles significantly enhanced the rate of Ca(2+)-dependent ATP hydrolysis. Maximal stimulation, observed with 100 units/mg vesicular protein, resulted in an ATPase activity which was about two folds over basal value. The same acylphosphatase concentration increased at a similar extent the rate of ATP driven Ca2+ influx into sarcoplasmic reticulum vesicles. Taken together these findings lead to suppose that acylphosphatase, owing to its hydrolytic activity, induces an accelerated turnover of the phosphoenzyme intermediate, whence an overall stimulation of heart sarcoplasmic reticulum Ca2+ pump, affecting both ATP hydrolysis and Ca2+ influx.
Biochem Mol Biol Int 1996 May
PMID:Acylphosphatase stimulates Ca2+ transport and Ca(2+)-dependent ATPase activity in cardiac sarcoplasmic reticulum. 879 67

PhoB is a response-regulator protein from Escherichia coli that controls an adaptive response to limiting phosphate. It is activated by autophosphorylation of a conserved aspartate residue within its regulatory domain. Its primary phospho-donor is its cognate histidine kinase PhoR; however, it also becomes phosphorylated when incubated with acetylphosphate. To further characterize its activation, PhoB was considered to be an acetylphosphatase whose enzymatic mechanism involves a phospho-enzyme intermediate. The kinetic constants for autophosphorylation were determined using 32P-and fluorescence-based assays and indicated that PhoB has a K(m) for acetylphosphate of between 7 and 8 mM. These constants are not consistent with an in vivo role for acetylphosphate in the normal control of the Pho regulon. In addition, when PhoB was phosphorylated by acetylphosphate it eluted from a high-performance liquid chromatography (HPLC) size-exclusion column in two peaks. The larger form of PhoB eluted from the column in a similar manner to a chemically cross-linked dimer of PhoB. The smaller form of PhoB is a monomer. Phosphorylated PhoB bound pho-box DNA approximately 10 times tighter than PhoB. These observations show that PhoB forms a dimer when phosphorylated and suggest that the characteristics of activated PhoB result from its dimerization.
Mol Microbiol 1996 Jun
PMID:The activation of PhoB by acetylphosphate. 880 68

A novel enzymatic activity on nucleic acids was discovered in both muscle type (MT) and erythrocyte or common type (CT) isoforms of acylphosphatase, an enzyme that was previously known as a hydrolase (E.C.3.6.1.7). Both deoxyribonucleic and ribonucleic hydrolitic activity were assayed on a variety of substrates. Our results demonstrate that acylphosphatase possesses both Mg++ dependent deoxyribonuclease and ribonuclease activities, at pH ranging from 5.0 to 6.8. Furthermore, we present evidences, for both isoenzymatic forms, of the coexistence of exonucleolytic and endonucleolytic activities on DNA.
Biochem Mol Biol Int 1996 Sep
PMID:Characterization of a novel nucleolytic activity of acylphosphatases. 888 72


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