ライフサイエンスコーパス: GlnRS

1 GlnRS is absent, however, in archaea, and most bacteria,

2 GlnRS(L136F) is more mischarging and less specific than

3 RS2 is a few steps away from evolving into a GlnRS and provides a paradigm for studying aminoacyl-tRN

4 Although GlnRS structures from two prokaryotic species are known,

5 iments demonstrate the presence of AsnRS and GlnRS, as well as glutamyl-tRNA synthetase (GluRS), a di

6 he crystallographic structures of GatCAB and GlnRS-tRNA complex from bacteria.

7 , and the resulting discriminating GluRS and GlnRS further acquired additional protein domains assist

8 the conserved bases and residues of tRNA and GlnRS are severely constrained in the global motions of

9 nd CysRS often have paralogs, whereas AsnRS, GlnRS, PylRS and SepRS are often absent from many genome

10 In the Bacteria, GlnRS genes have been identified in a total of 10 specie

11 Although all bacterial GlnRS form a monophyletic group, the broad phyletic dist

12 domains are absent in contemporary bacterial GlnRS and GluRS.

13 f an acceptor stem loop present in bacterial GlnRS.

14 the major sequence-specific contacts between GlnRS and tRNAGln.

15 he accuracy of specific interactions between GlnRS and tRNAGln determines amino acid affinity.

16 s suggest that specific interactions between GlnRS and tRNAGln ensure the accurate positioning of the

17 led comparison of kinetic parameters between GlnRS S1/L1/L2 and the naturally occurring Methanothermo

18 s demonstrate that amino acid specificity by GlnRS cannot arise from hydrogen bonds donated by the co

19 erate recognition of C34 and modified U34 by GlnRS.

20 inoacylation of tRNA(CUA)Tyr [tyrT (UAG)] by GlnRS-D235H resulted in a 4-fold increase in the Km for

21 Two crystal structures of this C229R GlnRS mutant reveal that a conserved twin-arginine GluRS

22 Importantly, S. cerevisiae GlnRS aminoacylates the yeast orthogonal tRNA in vitro a

23 lysis of the NTD of Saccharomyces cerevisiae GlnRS, Gln4.

24 The E. coli GlnRS coding sequence attached to a minimal mammalian ce

25 rus VP16 activation domain, with the E. coli GlnRS gene and the E. coli glutamine-inserting amber sup

26 acycline-regulated expression of the E. coli GlnRS gene and, thereby, tetracycline-regulated suppress

27 Plasmids carrying the E. coli GlnRS gene can be stably maintained in yeast.

28 ransactivator-mediated expression of E. coli GlnRS was essentially completely blocked in HeLa or COS-

29 domain is highly similar to Escherichia coli GlnRS but that 214 residues, including the NTD, are crys

30 R, improves the capacity of Escherichia coli GlnRS to synthesize misacylated Glu-tRNA(Gln) by 16,000-

31 licate the RNA component of the contemporary GlnRS-tRNA(Gln) complex in mediating amino acid specific

32 demonstrated the presence of the cytoplasmic GlnRS in the organelle and its involvement in mitochondr

33 rystallographic studies of several different GlnRS complexes in a lattice that supports catalytic act

34 prokaryotic species are known, no eukaryotic GlnRS structure has been reported.

35 The L136A/M/T/V mutants are the first GlnRS variants, including wild-type, expressed on pBR322

36 gene in eukaryotes gave rise to the gene for GlnRS-a copy of which was subsequently transferred to pr

37 d type and two pathological mutants of human GlnRS, which reveal, for the first time, the domain orga

38 The engineered hybrid (GlnRS S1/L1/L2) synthesizes Glu-tRNA(Gln) more than 10(4

39 ecognition to the acceptor binding domain in GlnRS.

40 Mutations in GlnRS at D235, which makes contacts with nucleotides in

41 Compound heterozygous mutations in GlnRS cause severe brain disorders by a poorly understoo

42 nt of other primary binding site residues in GlnRS, with those of GluRS, only slightly improves the a

43 e tertiary core of this tRNA plays a role in GlnRS recognition.

44 rentiated cognate amino acid-binding site in GlnRS may be a consequence of the late emergence of this

45 nd that the evolution of tRNA specificity in GlnRS could be recapitulated by converting the M. therma

46 loop-strand-helix connectivity subdomain in GlnRS has further implicated this domain in the function

47 E. coli aminoacyl-tRNA synthetase including GlnRS, and it functions efficiently in protein translati

48 entity signature cannot be incorporated into GlnRS without disrupting surrounding protein structural

49 The archaea lack GlnRS and use a specialized amidotransferase to convert

50 erform molecular dynamics on the full-length GlnRS-tRNA complex, which suggests that tRNA binding inv

51 owed by genetic selection resulted in mutant GlnRS enzymes that efficiently acylate the engineered tR

52 The mutant GlnRS and engineered tRNA also constitute a functional s

53 question to ask is whether, in the advent of GlnRS, a transient GluRS-like intermediate could have be

54 e enzyme modulate the amino acid affinity of GlnRS.

55 ars to be a transient GluRS-like ancestor of GlnRS and can be defined as a GluGlnRS.

56 als, fungi, and plants), the distribution of GlnRS genes in the Bacteria, and their evolutionary rela

57 ues in all three tRNA recognition domains of GlnRS, thus completing a survey of the major sequence-sp

58 re is still no evidence for the existence of GlnRS in the Archaea.

59 tRNA synthetase (GlnRS) improves the K(M) of GlnRS for noncognate glutamate.

60 examination of the global mode of motion of GlnRS in the complex indicates that residues 40 to 45, 2

61 Characterization of mutants of GlnRS at position 235, showed amino acid recognition to

62 6M, L136A, and L136T) mischarging mutants of GlnRS have been identified.

63 Also, unlike other mischarging mutants of GlnRS that have been characterized, it does not exhibit

64 er, questions remain about the occurrence of GlnRS genes among the Eucarya (eukaryotes) outside of th

65 ced catalytic efficiency and a propensity of GlnRS mutants to misfold trigger the disease development

66 decrease catalytic activity and stability of GlnRS, whereas missense mutations in the catalytic domai

67 -tRNA synthetase (GlnRS) is intriguing since GlnRS is primarily a eukaryotic enzyme, whereas in other

68 thway, while eukaryotes developed a specific GlnRS gene through the duplication of an existing GluRS

69 of the glutaminyl-tRNA aminoacyl synthetase (GlnRS)-tRNA2Gln complex and on previous biochemical data

70 include E. coli glutaminyl-tRNA synthetase (GlnRS) along with an amber suppressor derived from human

71 Escherichia coli glutaminyl-tRNA synthetase (GlnRS) along with the E. coli glutamine-inserting amber

72 n complexed with glutaminyl-tRNA synthetase (GlnRS) are in good agreement with the corresponding crys

73 cture of E. coli glutaminyl-tRNA synthetase (GlnRS) bound to native tRNA1(Gln) and ATP demonstrates t

74 does not have a glutaminyl-tRNA synthetase (GlnRS) but has two divergent glutamyl-tRNA synthetases:

75 ies of TrpRS and glutaminyl-tRNA synthetase (GlnRS) by mutagenesis without extensive, modular substit

76 Eukaryotic glutaminyl-tRNA synthetase (GlnRS) contains an appended N-terminal domain (NTD) whos

77 The glutaminyl-tRNA synthetase (GlnRS) enzyme, which pairs glutamine with tRNA(Gln) for

78 Glutaminyl-tRNA synthetase (GlnRS) evolved later and is derived from the archaeal-ty

79 Escherichia coli glutaminyl-tRNA synthetase (GlnRS) has revealed that the accuracy of specific intera

80 etase (GluRS) to glutaminyl-tRNA synthetase (GlnRS) improves the K(M) of GlnRS for noncognate glutama

81 Escherichia coli glutaminyl-tRNA synthetase (GlnRS) in complex with tRNAGln and ATP has identified a

82 Escherichia coli glutaminyl-tRNA synthetase (GlnRS) in complex with tRNAGln, leucine 136 (Leu136) sta

83 domain (NTD) of glutaminyl-tRNA synthetase (GlnRS) is intriguing since GlnRS is primarily a eukaryot

84 Glutaminyl-tRNA synthetase (GlnRS) is one noteworthy exception to the universality o

85 Cytosolic glutaminyl-tRNA synthetase (GlnRS) is the singular enzyme responsible for translatio

86 Escherichia coli glutaminyl-tRNA synthetase (GlnRS) proteins that incorrectly aminoacylate the amber

87 etic analyses of glutaminyl-tRNA synthetase (GlnRS) reveal that the enzyme discriminates against nonc

88 Escherichia coli glutaminyl-tRNA synthetase (GlnRS) were replaced with the corresponding residues of

89 mploy a specific glutaminyl-tRNA synthetase (GlnRS) which other Bacteria, the Archaea (archaebacteria

90 is catalyzed by glutaminyl-tRNA synthetase (GlnRS), while most bacteria, archaea, and chloroplasts e

91 ncluding E. coli glutaminyl-tRNA synthetase (GlnRS), yet functions with the E. coli translational mac

92 Escherichia coli glutaminyl-tRNA synthetase (GlnRS).

93 Escherichia coli glutaminyl-tRNA synthetase (GlnRS).

94 etase (AsnRS) or glutaminyl-tRNA synthetase (GlnRS).

95 l archaea lack a glutaminyl-tRNA synthetase (GlnRS); instead, Gln-tRNA(Gln) is produced via an indire

96 Escherichia coli glutaminyl-tRNA synthetase (GlnRS; EC 6.1.1.18) that the accuracy of tRNA recognitio

97 ) more than 10(4)-fold more efficiently than GlnRS.

98 Phylogenetic analyses predict that GlnRS arose from glutamyl-tRNA synthetase (GluRS), via g

99 Here, we show that GlnRS occurs in the most deeply branching eukaryotes and

100 Specifically, we analyzed the GlnRS determinants involved in recognition of the antico

101 ystal structures of unliganded GlnRS and the GlnRS-tRNA(Gln) complex reveal that the Glu34 and Glu73

102 ne and AMP must be directly catalyzed by the GlnRS x tRNA(2'HGln) complex.

103 otein domains assisting function in cis (the GlnRS N-terminal Yqey domain) or in trans (the Arc1p pro

104 S, only slightly improves the ability of the GlnRS active site to accommodate glutamate.

105 gand binding is essential to assembly of the GlnRS active site, these findings suggest a model for sp

106 The nature of the GlnRS mutations, which occur both at the protein-tRNA in

107 Crystal structures of the GlnRS x tRNA complex bound to either amino acid have pre

108 We infer that the GlnRS architecture has differentiated to match only cogn

109 fur moiety improves tRNA binding affinity to GlnRS 10-fold compared with the unmodified transcript an

110 s experiments showed that tRNA(Gln) binds to GlnRS approximately 60-fold weaker when noncognate gluta

111 containing G15-G48 were determined bound to GlnRS.

112 ution of archaeal nondiscriminating GluRS to GlnRS.

113 from the Archaea are more closely related to GlnRS and GluRS genes of the Eucarya than to those of Ba

114 35 are apparently the major binding sites to GlnRS, with G36 contributing both to binding and recogni

115 no acid activation suggests that the tRNAGln-GlnRS complex may be partly analogous to ribonucleoprote

116 hat GluRS2 is evolving into a bacterial-type GlnRS.

117 mischarging and less specific than wild-type GlnRS in vivo, due not to an increased affinity for the

118 The crystal structures of unliganded GlnRS and the GlnRS-tRNA(Gln) complex reveal that the Gl

119 he first crystallographic structure of yeast GlnRS, finding that the structure of the C-terminal doma

120 -derived suppressor tRNA together with yeast GlnRS thus represents a completely orthogonal tRNA/synth