ライフサイエンスコーパス: AdoMet

1 AdoMet binding is accompanied by a reorientation between

2 AdoMet formation is catalyzed by S-adenosylmethionine sy

3 AdoMet recycling from 5'-methylthioadenosine (MTA) was b

4 AdoMet-dependent methyltransferases belong to multiple d

5 stituent of the SET7/9.p53-Lys4-N(Me)H 2 (+).AdoMet complex.

6 (+).AdoHcy, or SET7/9.p53-Lys4-N(Me)H 2 (+).AdoMet complex.

7 The third methyl transfer (Lys-N(Me)2 + AdoMet --> Lys-N(Me)3+ + AdoHcy) is associated with an a

8 The third methylation [Lys27-N(Me)2 + AdoMet --> Lys27-N(Me)3+ + AdoHcy] is associated with a

9 he methyl transfer reaction [p53-Lys4-NH 2 + AdoMet --> p53-Lys4-N(Me)H 2 (+) + AdoHcy] in the SET7/9

10 conformation of the Enz.Lys-N(Me)H(2)(+).(+)AdoMet has the methyl positioned to block formation of a

11 solvent; then the reaction Enz.Lys-NH(2).(+)AdoMet --> Enz.Lys-N(Me)H(2)(+).AdoHcy occurs.

12 er formation of the SET7/9.p53-Lys4-NH 3 (+).AdoMet complex, the following events occur: (i) the appe

13 et species to provide an Enz.Lys-NH(3)(+).(+)AdoMet complex.

14 The 1.7 A structure of a AdoMet-bound CBS regulatory domain shows one AdoMet mole

15 S-adenosylmethionine (AdoMet or SAM)-dependent methyltransferases belong to a

16 % reduction in hepatic S-adenosylmethionine (AdoMet) (p < 0.01) and a 3-fold increase in hepatic S-ad

17 The S-adenosylmethionine (AdoMet) analog sinefungin is a natural product antibioti

18 for synthesis of both S-adenosylmethionine (AdoMet) and deoxythymidine monophosphate (dTMP), which a

19 ed by enzymes that use S-adenosylmethionine (AdoMet) as the methyl group donor.

20 iological methyl donor S-adenosylmethionine (AdoMet) can exist in two diastereoisomeric states with r

21 MoaA is a radical S-adenosylmethionine (AdoMet) enzyme that catalyzes a complex rearrangement of

22 .1.99.17) is a radical S-adenosylmethionine (AdoMet) enzyme that uses a [4Fe-4S](+) cluster to reduct

23 S-adenosylmethionine (AdoMet) lies at an intersection of nucleotide and amino

24 reaction steps in the S-adenosylmethionine (AdoMet) methylation of lysine-NH2 catalyzed by a methylt

25 anaerobic conditions, S-adenosylmethionine (AdoMet) radical chemistry is used.

26 a [4Fe-4S] cluster and S-adenosylmethionine (AdoMet) radical chemistry; the remainder of the reaction

27 This enzyme is an S-adenosylmethionine (AdoMet) radical enzyme that catalyzes the reductive clea

28 alamin (Cbl)-dependent S-adenosylmethionine (AdoMet) radical enzyme, OxsB, and an HD-domain phosphohy

29 The S-adenosylmethionine (AdoMet) radical superfamily of enzymes includes over 113

30 ferase domains for the S-adenosylmethionine (AdoMet) reactions.

31 The S-adenosylmethionine (AdoMet) salvage enzyme 5'-methylthioadenosine phosphoryl

32 member of the radical S-adenosylmethionine (AdoMet) superfamily and catalyzes the complex chemical r

33 of a methyl group from S-adenosylmethionine (AdoMet) to a peptidylarginine on a protein substrate.

34 yzes the conversion of S-adenosylmethionine (AdoMet) to ACC, the precursor of ethylene.

35 of methyl groups from S-adenosylmethionine (AdoMet) to acceptor lysine residues on histones and othe

36 a methyl transfer from S-adenosylmethionine (AdoMet) to dopamine.

37 enerated HMP when AIR, S-adenosylmethionine (AdoMet), and an appropriate reducing agent were present.

38 the PIMT co-substrate, S-adenosylmethionine (AdoMet), during panning permitted PIMT to retain aged ph

39 he Ki of MATalpha2 for S-adenosylmethionine (AdoMet), this allowed steady-state AdoMet level to rise.

40 ron-sulfur cluster and S-adenosylmethionine (AdoMet), thus placing it among the AdoMet radical superf

41 terically activated by S-adenosylmethionine (AdoMet), which binds to the regulatory domain and trigge

42 methyltransferases is S-adenosylmethionine (AdoMet), which in most cells is synthesized using methyl

43 S-adenosylmethionine (AdoMet)-based methylation is integral to metabolism and

44 Es are observed for an S-adenosylmethionine (AdoMet)-binary and abortive ternary complex containing 8

45 ransferases (KMTs) are S-adenosylmethionine (AdoMet)-dependent enzymes that catalyze the site-specifi

46 TrmA catalyzes S-adenosylmethionine (AdoMet)-dependent methylation of U54 in most tRNAs.

47 nd thymidylate and for S-adenosylmethionine (AdoMet)-dependent methylation reactions.

48 a mitochondrial human S-adenosylmethionine (AdoMet)-dependent methyltransferase and found it to meth

49 phosphocholine via two S-adenosylmethionine (AdoMet)-dependent phosphoethanolamine methyltransferases

50 Hcy), a product of all S-adenosylmethionine (AdoMet)-utilizing methyltransferase reactions.

51 to the methylation by S-adenosylmethionine (AdoMet).

52 tepwise methylation by S-adenosylmethionine (AdoMet).

53 n a reaction requiring S-adenosylmethionine (AdoMet).

54 e allosteric effector, S-adenosylmethionine (AdoMet); whereas T257M and T257I are inhibited, the othe

55 dical enzymes (GREs) by S-adenosylmethonine (AdoMet or SAM)-dependent enzymes has long been shown to

56 interactions are important for high-affinity AdoMet binding and transition-state stabilization.

57 lly demonstrated that we could thereby alter AdoMet pools and increase or decrease demand on folate a

58 Here, BtrN, an AdoMet radical dehydrogenase that catalyzes the two-elec

59 tion and reveal the ill-defined PfSET7 is an AdoMet-dependent histone H3 lysine methyltransferase wit

60 ctivating enzyme, the first structures of an AdoMet radical activase.

61 tridium perfringens are also the first of an AdoMet radical enzyme that performs dehydrogenase chemis

62 provides support for the establishment of an AdoMet radical structural motif that is likely common to

63 We report here that sinefungin (SIN), an AdoMet analog, inhibits several flaviviruses through sup

64 ltransferase reactions using both AdoHcy and AdoMet indicated that the assay tolerated 1 to 3 microM

65 Under optimized conditions, AdoHcy and AdoMet titrations demonstrated that the antibody had mor

66 PFL, PFL-AE, and AdoMet are essentially fully bound in vivo, whereas elec

67 formation that juxtaposes the cobalamin- and AdoMet-binding domains.

68 results suggest that heme incorporation and AdoMet regulation in CBS are not correlated, possibly pr

69 atode provides new insights on inhibitor and AdoMet/AdoCys binding to these enzymes.

70 omolecules using AdoMet-dependent MTases and AdoMet analogues.

71 0 nM folate led to imbalanced nucleotide and AdoMet pools only in cells with endogenously high polyam

72 ion of the damaged nucleosomes with PIMT and AdoMet.

73 enzyme affinity to the products of tRNA and AdoMet.

74 The enzyme reacts with Lys-NH(3)(+) and (+)AdoMet species to provide an Enz.Lys-NH(3)(+).(+)AdoMet

75 sently missing from our understanding of any AdoMet-dependent methyl-transfer reaction is a high-reso

76 S-Adenosylmethionine (SAM, also known as AdoMet) radical enzymes use SAM and a [4Fe-4S] cluster t

77 The data suggest that ICMT and Ma MTase bind AdoMet in a similar manner.

78 late depletion leads to an imbalance in both AdoMet and nucleotide pools, causing epigenetic and gene

79 The PFL-AE bound AdoMet with the same affinity ( approximately 6 muM) reg

80 alorimetry confirmed that each monomer bound AdoMet but with different binding affinities (K(d) = 52

81 h monomer of the homodimeric structure bound AdoMet in its active site.

82 we present the structure of hCBS with bound AdoMet, revealing the activated conformation of the huma

83 ses in the RlmH or COG1576 family with bound AdoMet.

84 er elucidate the chemistry of the burgeoning AdoMet radical superfamily in the future.

85 discuss the mechanism of hCBS activation by AdoMet and the properties of the AdoMet binding site, as

86 ervations demonstrate that CBS activation by AdoMet puzzlingly sensitizes the enzyme toward inhibitio

87 S rRNA, a conserved methylation catalyzed by AdoMet-dependent enzymes in all other characterized bact

88 binding to reduced CBS was also enhanced by AdoMet, although to a lesser extent ( approximately 2-fo

89 ted, the other mutants are hyperactivated by AdoMet.

90 The activity was inhibited by AdoMet metabolites S-adenosylhomocysteine, adenosine, 5'

91 ically highly active and is not regulated by AdoMet.

92 ted 2.9-, 2.5-, and 1.4-fold respectively by AdoMet.

93 antly, CO and NO(*) binding was unchanged by AdoMet in a truncated form of CBS lacking the C-terminal

94 N(Lys4), and the angle Sdelta(AdoMet)-Cgamma(AdoMet)-N(Lys4) determine whether methyl transfer can oc

95 ater distance (6.1 +/- 0.3 A) between Cgamma(AdoMet) and N(MeLys4) than is present in SET7/9.Lys4-NH3

96 ing a [4Fe-4S] cluster to reductively cleave AdoMet to form a transient 5'-deoxyadenosyl radical and

97 a [4Fe-4S](+) cluster to reductively cleave AdoMet to methionine and a 5'-deoxyadenosyl radical that

98 tant enzymes were able to reductively cleave AdoMet, but none were able to produce a significant amou

99 active site of SET7/ 9 opens up the cofactor AdoMet binding channel so that solvent water molecules g

100 ediated by a family of SET domain containing AdoMet-dependent enzymes.

101 Conversely, AdoMet binding stimulates CBS activity.

102 viously undescribed modification to the core AdoMet radical fold: instead of the canonical (beta/alph

103 al to intracellular levels of decarboxylated AdoMet (dcAdoMet).

104 of OxsB reveals the fold of a Cbl-dependent AdoMet radical enzyme, a family of enzymes with an estim

105 characterized non-methylating Cbl-dependent AdoMet radical enzyme.

106 ds the catalytic repertoire of Cbl-dependent AdoMet radical enzymes.

107 S-adenosyl-l-methionine (AdoMet), displayed AdoMet non-competitive and DNA competitive behavior.

108 The 2.64 A resolution protein/DNA/AdoMet structure of the inactive C81A M.HhaI mutant sugg

109 creases the recruitment of the methyl donor, AdoMet (S-adenosyl methionine), to RNMT.

110 To examine how BtrN employs AdoMet radical chemistry, we have determined its structu

111 (ii) substrate ionization to provide enzyme.AdoMet.Lys-NH2, and (iii) methyl transfer providing enzy

112 esolution structure of a precatalytic enzyme/AdoMet/DNA complex.

113 -containing 8-mer peptide substrate and 1 eq AdoMet, conditions that allow for the first sulfur inser

114 cluster binding region between BtrN, fellow AdoMet radical dehydrogenase anSME, and molybdenum cofac

115 ), Asp(444), Gln(445), and Asp(538)) and for AdoMet-driven inter-domain communication (Phe(443), Asp(

116 Heat capacity changes for AdoMet and AdoCys binding suggests that each HcPMT diffe

117 tely determine the equilibrium constants for AdoMet binding to PFL-AE alone and in complex with PFL.

118 by decreasing the affinity of the enzyme for AdoMet.

119 verified by mutagenesis to be important for AdoMet binding (Phe(443), Asp(444), Gln(445), and Asp(53

120 ic states that alter k(cat) but not K(m) for AdoMet.

121 Another mechanism for AdoMet synthesis uses betaine as the methyl donor via th

122 ate of 0.048 +/- 0.001 s(-1), with K(M)s for AdoMet and the p53 peptide of 0.031 +/- 0.01 muM and 0.6

123 enables the transfer of a methyl group from AdoMet to the cobalamin cofactor.

124 ocysts are unusual in being able to generate AdoMet not only by the ubiquitous folate-dependent mecha

125 the conformation of Enz.Lys-N(Me)(2)H(+).(+)AdoMet has a methyl in position, which forbids the forma

126 commonly used DNA labeling from [methyl-(3)H]AdoMet.

127 The structure of SET7/9.Lys4-N(Me)H2+.AdoMet includes a greater distance (6.1 +/- 0.3 A) betwe

128 this is not seen in the SET7/9.Lys4-N(Me)H2+.AdoMet species.

129 in the ground state of SET7/9.Lys4-N(Me)H2+.AdoMet, and the second methyl transfer does not occur.

130 cSHMT-deficient mice exhibit altered hepatic AdoMet levels and uracil content in DNA, validating prev

131 a mechanistic proposal is put forth for how AdoMet radical chemistry is coopted to perform a dehydro

132 channel into the aqueous solvent, and (iii) AdoMet methylation of p53-Lys4-NH 2 to form p53-Lys4-N(M

133 deletion within the conserved motif impaired AdoMet binding and significantly decreased enzymatic act

134 red ability of protozoan parasites to import AdoMet might determine sinefungin's anti-infective spect

135 ecreased polyamines but little alteration in AdoMet, methionine, or adenine levels.

136 Kinetic isotope effects in AdoMet-dependent methyltransferases may be mwedgeodulate

137 After four rounds, phage titer plateaued in AdoMet-containing pans, whereas titer declined in both c

138 that is not present in metal ion independent AdoMet decarboxylases from other organisms.

139 rochemistry, where the potential of both its AdoMet radical and auxiliary [4Fe-4S] clusters can be me

140 ich has sequence similarity with ICMT in its AdoMet binding site but methylates different substrates,

141 OrfX was crystallized in the presence of its AdoMet substrate, we found that each monomer of the homo

142 not appear for proton dissociation from LSMT.AdoMet.Lys-N(Me)2H+, and a third methyl transfer does no

143 tRNA anticodon, using S-adenosyl methionine (AdoMet) as the methyl donor.

144 the methyl group from S-adenosyl methionine (AdoMet) to the N1 position of G37 in tRNA to synthesize

145 binant TrmO employs S-adenosyl-L-methionine (AdoMet) as a methyl donor to methylate t(6)A to form m(6

146 )GpppAm-RNA), using S-adenosyl-l-methionine (AdoMet) as a methyl donor.

147 es use the cofactor S-adenosyl-l-Methionine (AdoMet) as a methyl source.

148 es are known to use S-adenosyl-l-methionine (AdoMet) as substrate; we have shown that 3',5'-cAMP bind

149 ogical methyl donor S-adenosyl-l-methionine (AdoMet) is spontaneously degraded by inversion of its su

150 cytosine C5 on the S-adenosyl-L-methionine (AdoMet) methyl group is concerted with formation of the

151 culans (BtrN) is an S-adenosyl-l-methionine (AdoMet) radical enzyme.

152 ethyl transfer from S-adenosyl-l-methionine (AdoMet) to glycine to form S-adenosyl-l-homocysteine and

153 d by the binding of S-adenosyl-l-methionine (AdoMet) to its regulatory domain, which activates its ca

154 a methyl group from S-adenosyl-L-methionine (AdoMet) to the 5-position of cytosine residues and there

155 methyl groups from S-adenosyl-L-methionine (AdoMet) to the epsilon-amino group of the target lysine

156 hyl donor cofactor, S-adenosyl-l-methionine (AdoMet), displayed AdoMet non-competitive and DNA compet

157 sulfonium center of S-adenosyl-L-methionine (AdoMet), generating methionine and a transient 5'-deoxya

158 th the methyl donor S-adenosyl-l-methionine (AdoMet), which is water-soluble, and the methyl acceptor

159 t it belongs to the S-adenosyl-L-methionine (AdoMet)-dependent alpha/beta-knot superfamily of SPOUT m

160 protein residues by S-adenosyl-L-methionine (AdoMet)-dependent methyltransferases impacts an array of

161 S-adenosyl-L-methionine (AdoMet)-dependent O-methyltransferases (OMTs) catalyze t

162 a methyl group from S-adenosyl-L-methionine (AdoMet).

163 trahydrofolate, and S-adenosyl-l-methionine (AdoMet).

164 inal domain binding S-adenosyl-l-methionine (AdoMet).

165 inescence assay for S-adenosyl-l-methionine (AdoMet/SAM)-based PMTs.

166 S-adenosyl-L-methionine- (AdoMet-) dependent methyltransferases are widespread, pl

167 cated that the assay tolerated 1 to 3 microM AdoMet.

168 maining plant versions have lost one or more AdoMet (SAM)-binding residues while preserving their sub

169 (0.15 pmol) AdoHcy in the presence of 3 muM AdoMet.

170 e report the synthesis and activity of a new AdoMet analogue functionalized with a ketone group.

171 sfer reaction catalyzed by vSET [Lys27-NH2 + AdoMet --> Lys27-N(Me)H2+ + AdoHcy] equals 22.5 +/- 4.3

172 transfer reaction in the SET7/9 [Lys4-NH2 + AdoMet --> Lys4-N(Me)H2+ + AdoHcy] complex is DeltaG++ =

173 (SET7/9.Lys4-NH3+.AdoMet --> SET7/9.Lys4-NH2.AdoMet + H+) must be prior to the methylation by S-adeno

174 ars in the presence of AdoMet (LSMT.Lys-NH3+.AdoMet), but is not present immediately after methyl tra

175 (MeLys4) than is present in SET7/9.Lys4-NH3+.AdoMet (5.7 +/- 0.2 A).

176 Proton dissociation (SET7/9.Lys4-NH3+.AdoMet --> SET7/9.Lys4-NH2.AdoMet + H+) must be prior to

177 A novel AdoMet binding assay was used to accurately determine th

178 ion, enzymes catalysing reactions of de novo AdoMet (MAT) and ornithine production (OrnPt) have more

179 78R-I, and P78R-II mutants in the absence of AdoMet are approximately 3-, 9-, and 3-fold lower than o

180 nalysis reveals that, even in the absence of AdoMet, the double mutant is locked in an activated conf

181 There is no water channel in the absence of AdoMet.

182 Finally, analogues of AdoMet are accepted by the regiocomplementary COMT mutan

183 Furthermore, thermodynamic analysis of AdoMet binding indicated that these interactions are imp

184 An array of AdoMet-dependent methyltransferases, Fe(II)- and alpha-k

185 Binding of AdoMet and AdoCys is tight (K(d) approximately 2-25 mum)

186 Binding of AdoMet triggers a conformational change in the Bateman m

187 re, TrmO/YaeB represents a novel category of AdoMet-dependent methyltransferase (Class VIII).

188 Two major classes of AdoMet analogues currently exist: doubly-activated molec

189 yme that catalyzes the reductive cleavage of AdoMet, generating methionine and a transient 5'-deoxyad

190 ignificant efforts toward the development of AdoMet analogues with the aim of transferring moieties o

191 nied by the reductive cleavage of 2 equiv of AdoMet.

192 nosine and binding of a second equivalent of AdoMet must be intermediate steps in the formation of bi

193 nine beta-synthase that result in failure of AdoMet-dependent regulation.

194 resents a convergent evolutionary feature of AdoMet-dependent methyltransferases, mediating a univers

195 ng behind the sulfur-bearing methyl group of AdoMet.

196 proposed to coordinate the methyl groups of AdoMet and methyllysine within the SET domain active sit

197 gen bonds with the ribose hydroxyl groups of AdoMet.

198 The impact of AdoMet binding and the pH dependence of catalysis are al

199 To examine the interaction of AdoMet and S-adenosylhomocysteine (AdoCys), isothermal t

200 framework for understanding the interplay of AdoMet and Cbl cofactors and expands the catalytic reper

201 ed the turnover rate and decreased the Km of AdoMet but did not affect the Km of the protein substrat

202 reduces the catalytic efficiency (kcat/Km of AdoMet) of ATXR5 up to 58-fold, highlighting the multifu

203 tion is run with substoichiometric levels of AdoMet or with the defective enzyme containing the Asn15

204 y SET7/9 histone lysine methyltransferase of AdoMet N-methylation of the transcriptional factor p53-L

205 The water channel appears in the presence of AdoMet (LSMT.Lys-NH3+.AdoMet), but is not present immedi

206 The water channel appears in the presence of AdoMet, but is not present in the species SET7/9.Lys4-NH

207 rved for wild-type enzyme in the presence of AdoMet, providing a structural rationale for loss of thi

208 In the presence of AdoMet, the autoinhibition exerted by the regulatory reg

209 s, which converged to one in the presence of AdoMet.

210 ma was directly correlated with the ratio of AdoMet to AdoHcy (P = 0.0001).

211 otent AdoMetDC inhibitors, several series of AdoMet substrate analogues with a variety of substituent

212 sitioned behind the methyl-bearing sulfur of AdoMet.

213 tives are presented for the potential use of AdoMet analogues in biology research, (epi)genetics and

214 een used to investigate the mechanisms of (+)AdoMet methylation of protein-Lys-NH(2) catalyzed by the

215 interactions between the positive charges on AdoMet and SET7/9.Lys4-NH3+ decrease the pKa of the latt

216 mine biosynthesis, due to the high demand on AdoMet pools, might be a factor in determining sensitivi

217 Since the BS active site holds only one AdoMet and one DTB, it follows that dissociation of meth

218 AdoMet-bound CBS regulatory domain shows one AdoMet molecule per monomer, at the interface between tw

219 ively cleave S-adenosyl-l-methionine (SAM or AdoMet) to generate a 5'-deoxyadenosyl radical that can

220 families of S-adenosyl-L-methionine (SAM or AdoMet)-dependent methyltransferases (MTs).

221 ted to be generally applicable to many other AdoMet-dependent enzymes.

222 de DNMTi that is also selective toward other AdoMet-dependent protein methyltransferases.

223 ) of CO to the ferrous heme at physiological AdoMet concentrations.

224 in a 75% reduction in methylation potential (AdoMet:AdoHcy) (p < 0.01).

225 accessory proteins, two of which are radical AdoMet enzymes (HydE, HydG) and one of which is a GTPase

226 oadenosine had been shown to inhibit radical AdoMet enzymes, suggesting that ThiC is distinct from ot

227 SPL is a member of the radical AdoMet superfamily of enzymes, and utilizes an iron-sulf

228 The radical-S-adenosylmethionine (radical-AdoMet) enzyme MiaB catalyzes the posttranscriptional me

229 Comparison of MiaB with other radical-AdoMet enzymes involved in thiolation reactions, such as

230 the three conserved cysteines in the radical-AdoMet motif (Cys150, Cys154, and Cys157) as previously

231 aG++ of the second methyl transfer reaction (AdoMet + Lys-N(Me)H --> AdoHcy + Lys-N(Me)2H+) at the QM

232 aG++ of the second methyl transfer reaction [AdoMet + Lys27-N(Me)H --> AdoHcy + Lys27-N(Me)2H+] at th

233 allosteric communication with the regulatory AdoMet-binding domain, and reveal the potential for inde

234 tituted in vitro, the ThiC reaction requires AdoMet, AIR, and reductant.

235 n of both genes results in significant (R,S)-AdoMet accumulation.

236 nzymes that are capable of recognizing (R,S)-AdoMet and using it to methylate homocysteine to form me

237 aneous intracellular generation of the (R,S)-AdoMet degradation product but for utilizing environment

238 Although the rate of (R,S)-AdoMet formation under physiological conditions is signi

239 We show that yeast cells can take up (R,S)-AdoMet from the medium using the same transporter (Sam3)

240 irst time that such an accumulation of (R,S)-AdoMet has been reported in any organism.

241 Unlike its precursor, (S,S)-AdoMet, (R,S)-AdoMet has no known cellular function and may have some

242 As of yet, (R,S)-AdoMet has no known physiological function and may inhib

243 unction to prevent the accumulation of (R,S)-AdoMet in these organisms.

244 are mechanisms that either dispose of (R,S)-AdoMet or convert it back to (S,S)-AdoMet.

245 e that Sam4 recognizes both (S,S)- and (R,S)-AdoMet, but that its activity is much higher with the R,

246 apable of recognizing and metabolizing (R,S)-AdoMet.

247 usly racemize to the R form, producing (R,S)-AdoMet.

248 Unlike its precursor, (S,S)-AdoMet, (R,S)-AdoMet has no known cellular function and

249 The S configuration, (S,S)-AdoMet, is the only form that is produced enzymatically

250 same transporter (Sam3) used to import (S,S)-AdoMet.

251 of (R,S)-AdoMet or convert it back to (S,S)-AdoMet.

252 ta(AdoMet) and N(Lys4), and the angle Sdelta(AdoMet)-Cgamma(AdoMet)-N(Lys4) determine whether methyl

253 a water channel, the distance between Sdelta(AdoMet) and N(Lys4), and the angle Sdelta(AdoMet)-Cgamma

254 azoan PRMT7 homologues in lacking the second AdoMet binding-like domain that is required for activity

255 thionine (AdoMet), this allowed steady-state AdoMet level to rise.

256 between 3',5'-cAMP and the native substrate AdoMet.

257 extended propargylic moieties from synthetic AdoMet cofactor analogs to duplex miRNAs or siRNAs.

258 We therefore propose that AdoMet-induced conformational change alters the interfac

259 We report that AdoMet binding significantly enhances CBS inhibition by

260 The AdoMet-dependent (or radical SAM) enzymes catalyze this

261 thionine (AdoMet), thus placing it among the AdoMet radical superfamily of enzymes.

262 hat these charged interactions formed by the AdoMet sulfonium cation are stronger than typical CH...O

263 hyltransferase encoded by TMT1 catalyzes the AdoMet-dependent monomethylation of 3-isopropylmalate, a

264 xygen (CH...O) hydrogen bonds coordinate the AdoMet methyl group in different methyltransferases irre

265 ght on active site architecture defining the AdoMet and phosphobase binding sites.

266 ntly linked to an adenosine moiety as in the AdoMet cofactor to generate transition state mimics.

267 t at least two of the three hydrogens in the AdoMet methyl group engage in CH ... O hydrogen bonding.

268 s intermodular contacts with residues in the AdoMet-binding module.

269 tivation by AdoMet and the properties of the AdoMet binding site, as well as the responsiveness of th

270 culations to examine the interactions of the AdoMet methyl group in the active site of the human KMT

271 O hydrogen bonds constrain the motion of the AdoMet methyl group, potentially facilitating its alignm

272 We find that the AdoMet radical cluster exhibits a midpoint potential of

273 In addition, the structure shows that the AdoMet-binding pocket, formed by a deep trefoil knot, co

274 erved hydrophobic pocket located next to the AdoMet-binding site.

275 ion between the two modules, relative to the AdoMet-free basal state, to form interactions with AdoMe

276 Hence, this AdoMet analogue expands the toolbox available to interro

277 More importantly, this AdoMet surrogate displays the same substrate specificity

278 nt that abolishes CH...O hydrogen bonding to AdoMet illustrate that these interactions are important

279 protein residues that form hydrogen bonds to AdoMet and DTB are important for retaining intermediates

280 ys kinetic parameters that are comparable to AdoMet and exhibits multiple turnovers with enzyme.

281 ld preference for binding AdoHcy relative to AdoMet.

282 d a noncompetitive inhibitor with respect to AdoMet, the methyl donor in the reaction.

283 We cover the synthetic routes to AdoMet analogues, their stability in biological environm

284 f wild-type enzyme but it is unresponsive to AdoMet, revealing that interactions between the two site

285 t is likely common to ~6,400 uncharacterized AdoMet radical enzymes.

286 hat contains homology to ~1,400 other unique AdoMet radical enzymes proposed to use [4Fe-4S] clusters

287 a pipette tip to quickly separate unreacted AdoMet from radiolabeled protein products.

288 on-overlapping pathways from their unrelated AdoMet families.

289 dicate a possible conformational change upon AdoMet/AdoCys binding.

290 mocysteine methyltransferases dependent upon AdoMet and S-methylmethionine, respectively.

291 lling and functionalizing biomolecules using AdoMet-dependent MTases and AdoMet analogues.

292 Polyamine biosynthesis also utilizes AdoMet, but polyamine pools are not reduced under a regi

293 7-N(Me)2H+ takes place upon combination with AdoMet.

294 own that 3',5'-cAMP binds competitively with AdoMet to the S. aureus TrmD protein, indicating an over

295 n crystal structure of PfPMT in complex with AdoMet by single-wavelength anomalous dispersion phasing

296 dies demonstrate that, upon interaction with AdoMet, active ThiC from Salmonella enterica generates a

297 -free basal state, to form interactions with AdoMet via residues verified by mutagenesis to be import

298 mbiguously support an ordered mechanism with AdoMet binding as the initial step, followed by the subs

299 are (i) combination of enzyme.Lys-NH3+ with AdoMet, (ii) substrate ionization to provide enzyme.AdoM

300 istry, we have determined its structure with AdoMet and substrate to 1.56 A resolution.

301 finding that increased gene dosage of yeast AdoMet synthase plus cap guanine-N7 methyltransferase af