ライフサイエンスコーパス: AANAT

1 AANAT activity in these cells was rhythmic in both LD an

2 AANAT activity is high at night in darkness, low during

3 AANAT expression and melatonin secretion (1) increased i

4 AANAT is a globular protein consisting of an eight-stran

5 AANAT is also found in the retina, where melatonin is th

6 AANAT is bound in the central channel of the 14-3-3zeta

7 AANAT peptides containing either T31 or S205 associate w

8 AANAT Thr31 phosphorylation on its own can enhance catal

9 AANATs from Agnathans (lamprey) and Chondrichthyes (cats

10 for accurate K D measurements of 14-3-3zeta-AANAT interaction using 14-3-3zeta fluorescently labeled

11 ivity of arylalkylamine N-acetyltransferase (AANAT) and N-acetylserotonin O-methyl transferase (ASMT)

12 Arylalkylamine N-acetyltransferase (AANAT) catalyzes the N-acetylation of serotonin, the pen

13 Serotonin N-acetyltransferase (AANAT) controls the daily rhythm in melatonin synthesis.

14 catalyzed by serotonin N-acetyltransferase (AANAT) in a reaction requiring acetyl coenzyme A (AcCoA)

15 Arylalkylamine N-acetyltransferase (AANAT) is the penultimate and key regulatory enzyme in t

16 -deficient aralkylamine N-acetyltransferase (AANAT) knockout mice.

17 sferase (arylalkylamine N-acetyltransferase (AANAT)) is a critical enzyme in the light-mediated regul

18 oxylase, arylalkylamine N-acetyltransferase (AANAT), and hydroxyindole-O-methyltransferase (HIOMT).

19 ivity of arylalkylamine N-acetyltransferase (AANAT), the penultimate enzyme in the melatonin pathway

20 gland by arylalkylamine N-acetyltransferase (AANAT), the penultimate enzyme in the synthesis of melat

21 tonin by arylalkylamine N-acetyltransferase (AANAT), which is predominantly expressed in the pineal g

22 g enzyme arylalkylamine N-acetyltransferase (AANAT).

23 hesis is arylalkylamine N-acetyltransferase (AANAT).

24 sferase [arylalkylamine N-acetyltransferase (AANAT)] is a key circadian rhythm enzyme that drives the

25 Arylalkylamine N-acetyltransferase (AANAT, serotonin N-acetyltransferase, EC ) plays a uniqu

26 nthesis, arylalkylamine N-acetyltransferase (AANAT; serotonin N-acetyltransferase, EC ).

27 ssion of arylalkylamine N-acetyltransferase (AANAT; the enzyme regulating melatonin synthesis) or inh

28 ssion of arylalkylamine N-acetyltransferase (AANAT; the rate-limiting enzyme for melatonin synthesis

29 sferase (arylalkylamine N-acetyltransferase, AANAT) in the pineal gland control the rhythmic producti

30 sferase (arylalkylamine N-acetyltransferase, AANAT) is a member of the GCN5 N-acetyltransferase (GNAT

31 sferase (arylalkylamine N-acetyltransferase, AANAT) mRNA in the chicken pineal gland exhibits a circa

32 ltransferase (serotonin N-acetyltransferase, AANAT, EC ) is the penultimate enzyme in melatonin synth

33 sferase (arylalkylamine N-acetyltransferase, AANAT, EC 2.3.1.87) is the first enzyme in the conversio

34 sferase (arylalkylamine N-acetyltransferase, AANAT, EC 2.3.1.87) is the penultimate enzyme in melaton

35 known as arylalkylamine N-acetyltransferase; AANAT) bound to a potent bisubstrate analog inhibitor ha

36 the dimeric 14-3-3 protein, which activates AANAT by increasing arylalkylamine affinity.

37 The pike AANAT-1 and AANAT-2 enzymes (66% identical amino acids) exhibit mark

38 These genes are designated AANAT-1 and AANAT-2; all known AANATs belong to the AANAT-1 subfamil

39 k between Ca(2+) influx, cAMP formation, and AANAT activity in retinal cells.

40 d light in the regulation of cAMP levels and AANAT activity in photoreceptor cells.

41 arly exclusively expressed in the retina and AANAT-2 in the pineal gland.

42 nd (2) effect of local modulation of biliary AANAT expression on the autocrine proliferative/secretor

43 and acetyltransferase reactions catalyzed by AANAT.

44 lly synthesized and found to be processed by AANAT, although 20- and 60-fold less efficiently compare

45 f melatonin, is acetylated from serotonin by AANAT (arylalkylamine N-acetyltransferase).

46 ontrol melatonin production without changing AANAT protein levels.

47 lar basis of the circadian rhythm in chicken AANAT (cAANAT).

48 nzymologic behavior of GST-AANAT and cleaved AANAT was essentially identical.

49 Within the complex, AANAT is catalytically activated and protected from deph

50 These genes are designated AANAT-1 and AANAT-2; all known AANATs belong to the AANA

51 nthesized and fused to bacterially expressed AANAT(30-199) using expressed protein ligation.

52 a lesser extent, BDL hepatocytes) expressed AANAT.

53 y complex (sequential) kinetic mechanism for AANAT and provide a framework for inhibitor design.

54 into the active site of X-ray structures for AANAT, and in total 241 compounds were tested as inhibit

55 ptamine were also shown to be substrates for AANAT, again with reduced kcat and kcat/Km compared with

56 o have enzyme activity generally typical for AANAT family members, although the substrate preference

57 the most striking difference is that fungal AANATs lack the regulatory domains of the vertebrate enz

58 sting genetic markers, 8 known genes (GALR2, AANAT, ENVL, SFRS2, SEC14L, DNAH17, API4, and TK1), and

59 ly expressed glutathione S-transferase (GST)-AANAT fusion protein.

60 The enzymologic behavior of GST-AANAT and cleaved AANAT was essentially identical.

61 endence on the H122Q, H120Q, and H120Q/H122Q AANAT mutants, we show that His-122 (with an apparent pK

62 bed here, a cell line (1E7) expressing human AANAT (hAANAT) has been developed to study the human enz

63 lead to the design of analogs with improved AANAT inhibitory properties for in vivo applications.

64 Large changes in AANAT activity play an important role in the daily rhyth

65 The decrease in AANAT expression, and subsequent lower melatonin secreti

66 ys displayed prominent daily fluctuations in AANAT activity on days 5 and 6 in vitro.

67 ated in wild-type C3H/f(+/+) mice but not in AANAT-mutated C57BL/6J mice, in a circadian rhythm; TrkB

68 thesis of melatonin; a large daily rhythm in AANAT activity drives the daily rhythm in circulating me

69 re describe a regulatory/binding sequence in AANAT that encodes a cAMP-operated binding switch throug

70 l regulation involves phosphorylation on key AANAT Ser and Thr residues which results in 14-3-3zeta r

71 re designated AANAT-1 and AANAT-2; all known AANATs belong to the AANAT-1 subfamily.

72 lso generated a doubly fluorescently labeled AANAT which can be used to assess the stability of this

73 hat binding of AANAT by 14-3-3zeta modulates AANAT's activity and affinity for its substrates by stab

74 cognized high-affinity 14-3-3-binding motifs AANAT protein binds to 14-3-3zeta through pT31 or pS205.

75 ion after a duplication of the nonvertebrate AANAT gene.

76 without markedly increasing the abundance of AANAT protein or the activity of AANAT in broken cell pr

77 bundance of AANAT protein or the activity of AANAT in broken cell preparations; and, that forskolin,

78 The activity of AANAT reflects changes in the amount and activation stat

79 Kinetic and structural analysis of AANAT has determined that one element is floppy.

80 lographic analysis, indicate that binding of AANAT by 14-3-3zeta modulates AANAT's activity and affin

81 switch from dual to single pS205 binding of AANAT to 14-3-3 changes the Km for substrates by approxi

82 Phosphorylation of T31 promotes binding of AANAT to the dimeric 14-3-3 protein, which activates AAN

83 To determine if circadian control of AANAT activity would develop in E6 cells incubated for a

84 appear to be causally related to control of AANAT activity.

85 Here, we focused on the evolution of AANAT in early vertebrates.

86 AANAT evolved from the nonvertebrate form of AANAT after the Cephalochordate-Vertebrate split over on

87 retinas from these groups express a form of AANAT that is compositionally, biochemically, and kineti

88 The nocturnal increase of AANAT activity also involves Ca(2+) influx, as it is inh

89 nhibitors suppress the nocturnal increase of AANAT in DD, while 8Br-cAMP augments it.

90 e first druglike and selective inhibitors of AANAT.

91 l molecules that are selective inhibitors of AANAT.

92 Kinetics of AANAT extracted from 1E7 cells are the same as those of

93 volves changes in the steady-state levels of AANAT protein.

94 In this study the kinetic mechanism of AANAT action was studied using bacterially expressed glu

95 stulated to be important in the mechanism of AANAT based on prior x-ray structural and biochemical st

96 of light/dark and circadian oscillations of AANAT activity in cultured retinal cells prepared from 6

97 Overexpression of AANAT in cholangiocyte cell lines decreased the basal pr

98 In vitro, overexpression of AANAT or inhibition of miR-200b in cholangiocytes and he

99 Phosphorylation of AANAT facilitates the binding of enzyme to 14-3-3 protei

100 ffects of single and dual phosphorylation of AANAT on acetyltransferase activity and relative affinit

101 t protein kinase-mediated phosphorylation of AANAT T31.

102 The products of AANAT activity were identified by RP-HPLC with fluorimet

103 or its substrates by stabilizing a region of AANAT involved in substrate binding.

104 n plays a critical role in the regulation of AANAT activity and melatonin production.

105 Development of light-dark regulation of AANAT activity appears to precede the circadian clock-co

106 e ability to express circadian regulation of AANAT activity is an intrinsic property of retinal cells

107 tend our understanding of cAMP regulation of AANAT activity, because it is currently thought that thi

108 role of Ca(2+) and cAMP in the regulation of AANAT activity.

109 for E6 cells displayed prominent rhythms of AANAT activity in both LD and DD, indicative of circadia

110 This unique essential role of AANAT in vertebrate timekeeping is recognized by the mon

111 ding to 14-3-3 and the cellular stability of AANAT and are consistent with the view that Ser-205 phos

112 We have determined the structure of AANAT bound to 14-3-3zeta, an association that is phosph

113 doleamine analogs as alternate substrates of AANAT.

114 The effect of light on AANAT activity was reversed by Bay K 8644, 8Br-cAMP, and

115 ding was also observed using humanized ovine AANAT, which has a different C-terminal sequence (Gly-Cy

116 to the three-dimensional structure of ovine AANAT catalytic core; however, an important structural e

117 These findings indicate that ovine AANAT is dual-phosphorylated.

118 scAANAT is 47% similar to ovine AANAT, but lacks the regulatory N- and C-terminal flanki

119 the dual anchoring of doubly phosphorylated AANAT via one 14-3-3zeta heterodimer.

120 Pike AANAT-1 is nearly exclusively expressed in the retina an

121 The pike AANAT-1 and AANAT-2 enzymes (66% identical amino acids)

122 Pineal AANAT activity increases at night in all vertebrates, re

123 -1 mRNA peaking in late afternoon and pineal AANAT-2 mRNA peaking 6 h later.

124 Here a putative AANAT from Saccharomyces cerevisiae (scAANAT) was studie

125 e analysis revealed the presence of putative AANATs in other fungi but not in the nearly complete gen

126 During the night in darkness, retinal AANAT is phosphorylated and forms a complex with 14-3-3

127 A changes on a circadian basis, with retinal AANAT-1 mRNA peaking in late afternoon and pineal AANAT-

128 In the current study, a putative second AANAT cyclic AMP-dependent protein kinase phosphorylatio

129 x enhances melatonin production by shielding AANAT from dephosphorylation and/or proteolysis and by d

130 Although a single AANAT gene has been found in mammals and the chicken, we

131 he middle of the subjective night suppressed AANAT activity, indicating that the enzyme activity in t

132 exposure at night, which rapidly suppresses AANAT activity, also suppressed cAMP levels.

133 tyltransferase, AA-NAT, HGMW-approved symbol AANAT; EC 2.3.1.87) is the penultimate enzyme in melaton

134 To accomplish this, a C-terminal AANAT peptide containing the phosphonodifluoromethylene

135 This result indicates that AANAT fluctuations were light-driven and not circadian a

136 Given a previous proposal that AANAT can catalyze an alkyltransferase reaction in a con

137 Furthermore, our data suggest that AANAT knockout mice are a model of accelerated aging.

138 and human BMAL1/MOP4 heterodimers bound the AANAT E box element and enhanced transcription.

139 Light disrupts the AANAT/14-3-3 complex, leading to catalytic inactivation,

140 , which may represent an intermediate in the AANAT degradation process.

141 Only vertebrate members of the AANAT family have been functionally characterized.

142 es in the amount and activation state of the AANAT protein, both of which increase at night.

143 and AANAT-2; all known AANATs belong to the AANAT-1 subfamily.

144 Formation of this AANAT/14-3-3 complex enhances melatonin production by sh

145 When isolated from tissue, AANAT copurifies with isoforms epsilon and zeta of 14-3-

146 ta demonstrate that the binding of 14-3-3 to AANAT is regulated by light, with dramatic functional co

147 Similar to AANAT activity, cAMP levels fluctuate in a daily fashion

148 y, biochemically, and kinetically similar to AANATs found in bony vertebrates (VT-AANAT).

149 ts the aryl-alkylamine-N-acetyl transferase (AANAT) fold, which is unprecedented in NRPS biology.

150 Two AANAT genes also exist in another fish, the trout.

151 and the chicken, we have now identified two AANAT genes in fish.

152 The evolution of two AANATs may represent a strategy to optimally meet tissue

153 ferase (arylalkylamine N-ace-tyltransferase (AANAT)) catalyzes the reaction of serotonin (or tryptami

154 experiments, as compared with the unmodified AANAT.

155 flanking regions conserved in all vertebrate AANATs.

156 In vivo, AANAT activity in chicken retinal photoreceptor cells ex

157 In chicken retina in vivo, AANAT is expressed in a circadian fashion, primarily in

158 The emergence of VT-AANAT apparently involved a dramatic acceleration of evo

159 nt with the hypotheses that the advent of VT-AANAT contributed to the evolution of the pineal gland a

160 volutionary rate estimation indicate that VT-AANAT evolved from the nonvertebrate form of AANAT after

161 n of the available genomes indicates that VT-AANAT is absent from other forms of life, including the

162 ilar to AANATs found in bony vertebrates (VT-AANAT).

163 ecreased in normal and BDL rats treated with AANAT Vivo-Morpholino, compared to controls.

164 The X-ray crystal structure of Y168F AANAT bound to a bisubstrate analog inhibitor showed no

165 Paradoxically, Y168F AANAT showed 10-fold enhanced apparent affinity for acet

166 By analysis of the Y168F AANAT mutant, it was demonstrated that Tyr-168 contribut