ライフサイエンスコーパス: PRMT

1 PRMTs are a family of proteins that either monomethylate

2 PRMTs are lost from the flagella of fla10-1 cells, which

3 PRMTs catalyze the transfer of a methyl group from S-ade

4 PRMT1 is the major type 1 PRMT in vivo, thus it is the primary producer of the com

5 Ts produce monomethyl arginine (MMA), type 1 PRMTs go on to form asymmetrically dimethylated arginine

6 3) and protein arginine methyltransferase 1 (PRMT-1) cooperate to orchestrate a series of posttransla

7 in a variety of cellular processes, aberrant PRMT activity is associated with several disease states,

8 Although all PRMTs produce monomethyl arginine (MMA), type 1 PRMTs go

9 ave a unique structure and specificity among PRMTs for methylating SF3B2 and potentially other polype

10 xamples have been reported of both PKMTs and PRMTs that are genetically altered in specific human can

11 nown, however, about the role of SWI/SNF and PRMTs in vitamin D receptor (VDR)-mediated transcription

12 Another PRMT, PRMT7, also affects SDMA levels at the same site d

13 We demonstrate that a major T. brucei PRMT, TbPRMT1, functions as a heterotetrameric enzyme-pr

14 cumulation occurs via increased synthesis by PRMTs and decreased degradation.

15 Most current PRMT inhibitors display limited specificity and selectiv

16 Attempts to develop PRMT inhibitors using receptor-based computational metho

17 s that have been generated against different PRMT substrates, and can also be used to confirm the pan

18 We found that we could distinguish PRMT family members by their sensitivity to these reagen

19 ermal progenitors and the most downregulated PRMT during differentiation.

20 lucidating the substrate specificity of each PRMT will promote a better understanding of which signal

21 ze such methylation reactions in eukaryotes (PRMTs) works in conjunction with a changing cast of asso

22 T1 was found to be the most highly expressed PRMT in epidermal progenitors and the most downregulated

23 ys automethylation activity; it is the first PRMT to do so.

24 rst demonstration of an obligate heteromeric PRMT, and they suggest that enzyme-prozyme organization

25 This novel human PRMT, which resides solely in the nucleus when fused to

26 Among the nine known human PRMTs, PRMT3 has been implicated in ribosomal biosynthes

27 se fusion protein, PRMT6 demonstrates type I PRMT activity, capable of forming both omega-N(G)-monome

28 ansferase fusion protein of PRMT8 has type I PRMT activity, catalyzing the formation of omega-NG-mono

29 maintaining the holo structure of the type I PRMT catalytic domain.

30 ly, Tyr(154) is also conserved in the type I PRMT family of enzymes, suggesting a general role of thi

31 to aspartate converts TbPRMT7 into a type I PRMT, producing asymmetric dimethylarginine (ADMA).

32 ed on 4, a fragment-like inhibitor of type I PRMTs, we conducted structure-activity relationship (SAR

33 ar, the most successful strategy to identify PRMT inhibitors has been to screen large to medium-size

34 ited abundant expression of PRMT5, a type II PRMT enzyme that promotes transcriptional silencing of t

35 PRMT5, a type II PRMT that interacts with BRG1, repressed Cyp24a1 transcr

36 dimethylarginine (SDMA) residues as type II PRMTs.

37 y representing the only exclusively type III PRMT identified to date.

38 studies indicate that TbPRMT7 is a Type III PRMT, and its robust activity and presence in numerous c

39 ubstrates reveals that TbPRMT7 is a type III PRMT, catalyzing the formation of only monomethylarginin

40 ubstrates, thus classifying it as a type III PRMT.

41 d a general model for product specificity in PRMTs, which will be useful for the rational design of s

42 The inactive PRMT paralog, TbPRMT1(PRO), is essential for catalytic a

43 velopment of inhibitors targeting individual PRMTs, we initiated studies to characterize the molecula

44 gher inhibition activity than the well-known PRMT inhibitors AMI-1.

45 PRMT5 is the main PRMT responsible for symmetric dimethylation of arginine

46 thyltransferase activity of PRMT1, the major PRMT isoform in humans, is impaired under oxidative cond

47 The expression of one of the nine mammalian PRMTs, PRMT5, affects the levels of symmetric dimethylar

48 Although many PRMT substrates have been identified, and their methylat

49 idues by protein arginine methyltransferase (PRMT) 1 and PRMT5 in its RGG domain.

50 Protein arginine methyltransferase (PRMT) 8 is unique among the PRMTs, as it has a highly re

51 Human protein arginine methyltransferase (PRMT) 9 symmetrically dimethylates arginine residues on

52 Protein arginine methyltransferase (PRMT) activity has been implicated in stem cell pluripot

53 onserved protein arginine methyltransferase (PRMT) catalytic core flanked by unique pre- and post-cor

54 for the protein arginine methyltransferase (PRMT) enzymes that catalyze these reactions has been lac

55 r of the protein arginine methyltransferase (PRMT) family and methylates a range of proteins in eukar

56 e type I protein arginine methyltransferase (PRMT) family of enzymes.

57 s of the protein arginine methyltransferase (PRMT) family: PRMT1, PRMT3, and PRMT6.

58 T7) is a protein arginine methyltransferase (PRMT) that strictly monomethylates various substrates, t

59 type II protein arginine methyltransferase (PRMT) that, in winter-annual strains, is required for ep

60 ed human protein-arginine methyltransferase (PRMT), was cloned and expressed in Escherichia coli and

61 nding to protein arginine methyltransferase (PRMT)-1, and nuclear asymmetrical dimethylarginine modif

62 nhibit protein arginine N-methyltransferase (PRMT) activity.

63 me for protein arginine N-methyltransferase (PRMT) family members, a novel gene has been found on chr

64 of the protein arginine N-methyltransferase (PRMT) family of enzymes has identified a gene on chromos

65 ype I protein arginine N-methyltransferases (PRMT), has been known for some time, members of this enz

66 used on protein arginine methyltransferases (PRMTs) 1, 3, 5, and 10.

67 Protein arginine methyltransferases (PRMTs) affect many processes; however, their role in pro

68 Protein arginine methyltransferases (PRMTs) aid in the regulation of many biological processe

69 dues by protein arginine methyltransferases (PRMTs) and is degraded by dimethylarginine dimethylamino

70 Protein arginine methyltransferases (PRMTs) are (S)-adenosylmethionine (SAM)-dependent methyl

71 The protein arginine methyltransferases (PRMTs) are a family of enzymes that catalyze the mono- a

72 Protein arginine methyltransferases (PRMTs) are a group of eukaryotic enzymes that catalyze t

73 The arginine methyltransferases (PRMTs) are envisaged as promising druggable targets, but

74 Protein arginine methyltransferases (PRMTs) are enzymes that are involved in many biological

75 tors of protein arginine methyltransferases (PRMTs) are invaluable chemical tools for testing biologi

76 Protein arginine methyltransferases (PRMTs) are proved to play vital roles in chromatin remod

77 Protein arginine methyltransferases (PRMTs) are SAM-dependent enzymes that catalyze the mono-

78 tion of protein arginine methyltransferases (PRMTs) has been linked to many pathological conditions.

79 Protein arginine methyltransferases (PRMTs) have been implicated in transcriptional activatio

80 Protein arginine methyltransferases (PRMTs) have emerged as attractive therapeutic targets fo

81 ones by protein arginine methyltransferases (PRMTs) impacts genome organization and gene expression.

82 s), and protein arginine methyltransferases (PRMTs) in pancreatic alpha- and beta-cell lines.

83 The protein arginine methyltransferases (PRMTs) include a family of proteins with related putativ

84 Protein arginine methyltransferases (PRMTs) introduce arginine methylation, a post-translatio

85 on by protein N-arginine methyltransferases (PRMTs) is an important posttranslational modification in

86 tion of protein arginine methyltransferases (PRMTs) is correlated with many human diseases.

87 atin by protein arginine methyltransferases (PRMTs) is crucial for normal cell growth and health.

88 Protein arginine methyltransferases (PRMTs) mediate the AdoMet-dependent methylation of many

89 Protein arginine methyltransferases (PRMTs) mediate the transfer of methyl groups to arginine

90 Protein arginine methyltransferases (PRMTs) play an important role in diverse biological proc

91 Protein arginine methyltransferases (PRMTs) play important roles in several cellular processe

92 Protein arginine methyltransferases (PRMTs) represent an emerging target class in oncology an

93 yzed by protein arginine methyltransferases (PRMTs) that are typically thought to function as homodim

94 mily of protein arginine methyltransferases (PRMTs) that predominantly generate either asymmetric or

95 mbinant protein arginine methyltransferases (PRMTs), we showed that the C-terminal domain could be me

96 mily of protein arginine methyltransferases (PRMTs).

97 include protein arginine methyltransferases (PRMTs).

98 Ts) and protein arginine methyltransferases (PRMTs).

99 lex and protein-arginine methyltransferases (PRMTs).

100 and the protein arginine methyltransferases (PRMTs).

101 ndent protein arginine N-methyltransferases (PRMTs) catalyze the methylation of arginine residues wit

102 evelopment and application of small molecule PRMT inhibitors will provide new avenues for therapeutic

103 he optimal target motif for each of the nine PRMTs has not been systematically addressed.

104 cule directly targets the substrates but not PRMTs for the observed inhibition.

105 These findings about novel PRMT inhibitors and their unique inhibition mechanism pr

106 for proteomic applications to identify novel PRMT substrates.

107 Accurate control of PRMT activity includes recognition of specific arginyl g

108 an serve as a warhead for the development of PRMT chemical probes.

109 To aid the development of PRMT inhibitors, we characterized the substrate specific

110 cate that motions are a conserved element of PRMT function.

111 ate bisubstrate analogue-based inhibitors of PRMT isozymes that are potent and highly selective for a

112 hromatography combined with the knowledge of PRMT crystal structures suggests a model where the size

113 to characterize the molecular mechanisms of PRMT catalysis.

114 Given the transient nature of PRMT-substrate complexes, such transition state mimics r

115 Aberrant regulation of PRMT activity is associated with various pathological st

116 implications for the rational (re)design of PRMTs.

117 These results suggest that native forms of PRMTs can have different properties than their GST-catal

118 However, few selective inhibitors of PRMTs have been discovered.

119 ific compounds that block the interaction of PRMTs with their targets.

120 so suggest a general model for regulation of PRMTs.

121 ion tag affects the substrate selectivity of PRMTs.

122 ossible overlapping substrate specificity of PRMTs, 17 and 46 are valuable chemical tools for dissect

123 the biological roles in cells and in vivo of PRMTs.

124 Inhibition of GSK3 or PRMT-1 or overexpression of the AC-associated mutant R28

125 nine protein arginine methyltransferases, or PRMTs.

126 ow that these motions are conserved in other PRMT enzymes.

127 of a catalytic core sequence common to other PRMT enzymes.

128 light differences between AtPRMT10 and other PRMTs but also indicate that motions are a conserved ele

129 3 substrate that cannot be modified by other PRMTs.

130 e region (C-extension), not present in other PRMTs.

131 intracellular signaling, the roles of other PRMTs in diverse cellular processes have not been fully

132 was selective for PRMT4 and PRMT6 over other PRMTs and a broad range of other epigenetic modifiers an

133 ore than hundred-fold selectivity over other PRMTs.

134 cus on its N-terminus and predict that other PRMTs may employ similar mechanism for substrate recogni

135 ontrast to what had been observed with other PRMTs and their physiological substrates, a peptide cont

136 Here, by deconstructing potent PRMT inhibitors, we find that chemical moieties occupyin

137 The predominant PRMT in vivo, PRMT1, has wide substrate specificity and

138 Trypanosoma brucei, possesses five putative PRMTs, a relatively large number for a single-celled euk

139 e useful for the rational design of specific PRMT inhibitors.

140 The data define the distribution of specific PRMTs and their target proteins in flagella and demonstr

141 However, cleavage of tagged PRMTs has been problematic.

142 recognition, it is imperative that a tagless PRMT be used.

143 resolution crystal structure of A. thaliana PRMT 10 (AtPRMT10) in complex with a reaction product, S

144 ation arm that is 12-20 residues longer than PRMT structures elucidated previously; as a result, the

145 In addition, we found that PRMT 1 and 3 are also highly enriched at the base of the

146 et proteins in flagella and demonstrate that PRMTs are cargo for translocation within flagella by the

147 up the active site are conserved across the PRMT family, consisting of a double-E loop containing tw

148 ct biological outputs, as highlighted in the PRMT-dependent epigenetic control of transcription.

149 As the only known member of the PRMT enzyme family to catalyze the formation of mono- an

150 of AtPRMT10, as well as other members of the PRMT family of enzymes.

151 basis for functional characterization of the PRMT family.

152 thyltransferase (PRMT) 8 is unique among the PRMTs, as it has a highly restricted tissue expression p

153 uct formation by active site residues in the PRMTs.

154 cterize the mechanisms and regulation of the PRMTs and develop chemical probes targeting these enzyme

155 ted the methylation efficiency of all of the PRMTs toward HMGA1 proteins.

156 These PRMTs localize to the tip of flagella and in a punctate

157 lagella, and the basal localization of these PRMTs changes during flagellar regeneration and resorpti

158 The predominant methyl transferase PRMT-1 is highly expressed in T helper cells, and ligati

159 report the characterization of a trypanosome PRMT, TbPRMT7, which is homologous to human PRMT7.

160 and are structurally different from typical PRMT substrates, for example, histone H4 and glycine- an

161 eloped a successful method by which untagged PRMTs can be made using a tobacco etch virus (TEV) cleav

162 To explore whether PRMTs modulate p53 function, we generated multiple cell

163 rucial to understand the mechanisms by which PRMT product specificity is conferred.