ライフサイエンスコーパス: methylmalonyl-CoA

1 complex with an inert thioether analogue of methylmalonyl CoA.

2 fold increase in the K(M) for the substrate, methylmalonyl-CoA.

3 tion, has been solved bound to its substrate methylmalonyl-CoA.

4 ochemical selectivity of the enzyme for (2R)-methylmalonyl-CoA.

5 -TE does not catalyze the decarboxylation of methylmalonyl-CoA.

6 tibiotic erythromycin from propionyl-CoA and methylmalonyl-CoA.

7 l-CoA and propionyl-CoA over malonyl-CoA and methylmalonyl-CoA.

8 talyzes the conversion of propionyl-CoA to D-methylmalonyl-CoA.

9 esis in Escherichia coli is the lack of (2S)-methylmalonyl-CoA, a common substrate of multimodular po

10 te, and the Rv0158 protein directly binds to methylmalonyl-CoA, a key intermediate in propionate cata

11 se (AT/DC) that derives propionyl-S-ACP from methylmalonyl-CoA, accounting for the missing link of th

12 this problem, we have synthesized a panel of methylmalonyl-CoA analogs with the carboxylate represent

13 ing in the EPR signals produced by [2'-(13)C]methylmalonyl-CoA and [2-(13)C]methylmalonyl-CoA as well

14 lonyl-CoA mutase in complexes with substrate methylmalonyl-CoA and inhibitors 2-carboxypropyl-CoA and

15 tify mutations in ACSF3, encoding a putative methylmalonyl-CoA and malonyl-CoA synthetase as a cause

16 etide lactone required the presence of (2RS)-methylmalonyl-CoA and NADPH.

17 he fumarate needed for alkane activation via methylmalonyl-CoA and predicted the capability for syntr

18 Methylmalonyl-CoA and succinyl-CoA are hydrolyzed and th

19 MCM interconverts (2R)-methylmalonyl-CoA and succinyl-CoA.

20 -CoA mutase catalyzes the interconversion of methylmalonyl-CoA and succinyl-CoA.

21 dependent decarboxylation of malonyl-CoA and methylmalonyl-CoA and the hydrolysis of CoA esters such

22 ependent on the enzymatic decarboxylation of methylmalonyl-CoA and transfer of the acyl chain within

23 acid, which is formed from the MCM substrate methylmalonyl-CoA and which inhibits succinate dehydroge

24 oxylated CoA thioester (e.g., malonyl-CoA or methylmalonyl-CoA) and an acyl carrier protein (ACP).

25 yn-(2S,3R)-2-methyl-3-hydroxypentanoate (6), methylmalonyl-CoA, and NADPH resulting in the exclusive

26 noyl-N-acetylcysteamine thioester (2b-SNAC), methylmalonyl-CoA, and NADPH with DEBS [KS6][AT6], DEBS

27 cubation of a mixture of propionyl-SNAC (4), methylmalonyl-CoA, and NADPH with the DEBS beta-ketoacyl

28 2S,3R)-2-methyl-3-hydroxypentanoyl-SNAC (5), methylmalonyl-CoA, and NADPH with the recombinant [KS6][

29 of reactions that require benzoate, Mg.ATP, methylmalonyl-CoA, and NADPH.

30 ss isotopomer distribution of propionyl-CoA, methylmalonyl-CoA, and succinyl-CoA in tissues.

31 s isotopomer distributions of propionyl-CoA, methylmalonyl-CoA, and succinyl-CoA revealed that, in in

32 CarB was also shown to accept methylmalonyl CoA as a substrate to form 6-methyl-(2S,5S

33 that ascomycin AT8 does not use malonyl- or methylmalonyl-CoA as a substrate in its native context.

34 rified sacogolassan protein EcPKS1 uses only methylmalonyl-CoA as a substrate, otherwise unknown in a

35 ed to enable the loading AT domain to accept methylmalonyl-CoA as an alternative substrate.

36 etylcysteamine-activated diketides and (14)C-methylmalonyl-CoA as substrates.

37 l-pyrroline-5-carboxylate and malonyl-CoA or methylmalonyl-CoA as the CoA esters of (2S,5S)-5-carboxy

38 erate triketide lactone products using (14)C-methylmalonyl-CoA as the sole substrate.

39 by [2'-(13)C]methylmalonyl-CoA and [2-(13)C]methylmalonyl-CoA as well as line narrowing resulting fr

40 coli strain produced both propionyl-CoA and methylmalonyl-CoA at intracellular levels similar to tho

41 s from Streptomyces coelicolor, which enable methylmalonyl-CoA biosynthesis.

42 Such multienzymes typically use malonyl and methylmalonyl-CoA building blocks for polyketide chain a

43 f isobutyryl-coenzyme A (isobutyryl-CoA) and methylmalonyl-CoA catalysed by a 3-ketoacyl-(acyl carrie

44 The apparent K(m) for (2S)-methylmalonyl-CoA consumption by DEBS 1+TE is 24 microM.

45 The molecular structure of methylmalonyl CoA decarboxylase (MMCD), a newly defined

46 The identification of YgfG as methylmalonyl CoA decarboxylase expands the range of rea

47 We have determined that YgfG is methylmalonyl CoA decarboxylase, YgfH is propionyl CoA:s

48 Structures of Escherichia coli methylmalonyl-CoA decarboxylase in complex with our anal

49 ncluding enoyl-CoA hydratase (crotonase) and methylmalonyl-CoA decarboxylase.

50 yl-CoA and propionyl-CoA carboxylases and of methylmalonyl-CoA decarboxylase.

51 nucleophilic attack of the carboxyl group in methylmalonyl-CoA does not appear to depend on interacti

52 ethylmalonyl-CoA racemase reaction keeps the methylmalonyl-CoA enantiomers in isotopic equilibrium un

53 ce; overexpression of NADH dehydrogenase and methylmalonyl-CoA epimerase improved PA tolerance.

54 omerizations (glyoxalase I), epimerizations (methylmalonyl-CoA epimerase), oxidative cleavage of C-C

55 ng glyoxalase I, extradiol dioxygenases, and methylmalonyl-CoA epimerase.

56 four extender units were known: malonyl-CoA, methylmalonyl-CoA, ethylmalonyl-CoA, and methoxymalonyl-

57 t elongation of the n-C20 acyl primer by one methylmalonyl-CoA extender unit was catalyzed by fatty a

58 one propionyl-CoA starter unit and six (2S)-methylmalonyl-CoA extender units.

59 S do not influence epimerization of the (2S)-methylmalonyl-CoA extender units.

60 Here we report a route for synthesizing (2S)-methylmalonyl-CoA from malonyl-CoA with a 3-hydroxypropi

61 y homogeneous synthase exhibits an intrinsic methylmalonyl-CoA hydrolase activity, which competes wit

62 We find that metabolic deficiency of methylmalonyl-CoA impedes the growth of PDIM-producing b

63 simple precursors such as propionyl-CoA and methylmalonyl-CoA in a biosynthetic process that closely

64 he component activities show selectivity for methylmalonyl-CoA in any biological system.

65 already contained methyl-branched FAs due to methylmalonyl-CoA incorporation, but these FAs were only

66 h the cellular pool of propionate and, thus, methylmalonyl CoA increasing upon cholesterol metabolism

67 0-kDa protein inhibited the incorporation of methylmalonyl-CoA into fatty acids by SMAS.

68 methylmalonyl-CoA the ability to incorporate methylmalonyl-CoA into fatty acids.

69 rboxylate group of the thioether analogue of methylmalonyl CoA is hydrogen bonded to the peptidic NH

70 is 0.84 min-1, and the apparent Km for (2RS)-methylmalonyl-CoA is 17 microM.

71 Therefore, although neither malonyl-CoA nor methylmalonyl-CoA is a substrate for ascomycin AT8 in it

72 Methylmalonyl-CoA is M3 and M2 labeled, reflecting rever

73 Decarboxylation of methylmalonyl-CoA is negligible in the presence of satur

74 active site, the labile carboxylate group of methylmalonyl-CoA is stabilized by interaction with the

75 iciency in the enzymes P-CoA carboxylase and methylmalonyl-CoA (M-CoA) mutase, respectively.

76 log of the natural ACP-bound substrate, with methylmalonyl-CoA (MM-CoA) in the absence of NADPH gave

77 Da hexamer that transfers carboxlylate from methylmalonyl-CoA (MM-CoA) to biotin; in turn, the bioti

78 ate reasonably well with those predicted for methylmalonyl-CoA (mMCoA) ATs.

79 o-crystallization with malonyl-CoA (MCoA) or methylmalonyl-CoA (MMCoA) led to partial turnover of the

80 zes the transfer of a carboxylate group from methylmalonyl-CoA (MMCoA) to pyruvate.

81 the vitamin B12 (cobalamin)-dependent enzyme methylmalonyl CoA mutase.

82 yl CoA:succinate CoA transferase, and Sbm is methylmalonyl CoA mutase.

83 Inherited defects in the gene for methylmalonyl-CoA mutase (EC 5.4.99.2) result in the mut

84 he presence and absence of nucleotides) with methylmalonyl-CoA mutase (in the presence and absence of

85 significant amino acid sequence identity to methylmalonyl-CoA mutase (MCM) (40%) and isobutyryl-CoA

86 tive 5'-deoxyadenosylcobalamin cofactor onto methylmalonyl-CoA mutase (MCM) and precludes loading of

87 tive, itaconyl-CoA, inhibits B(12)-dependent methylmalonyl-CoA mutase (MCM) by an unknown mechanism.

88 The methylmalonyl-CoA mutase (MCM) cDNA was highly expressed

89 Within this family, methylmalonyl-CoA mutase (MCM) is the best studied and i

90 mans, deficiencies in coenzyme B12-dependent methylmalonyl-CoA mutase (MCM) lead to methylmalonyl aci

91 of bacterial and mitochondrial B12-dependent methylmalonyl-CoA mutase (MCM), HCM has a highly conserv

92 osylcobalamin (AdoCbl or coenzyme B(12)), to methylmalonyl-CoA mutase (MCM), resulting in holoenzyme

93 he delivery of adenosylcobalamin (AdoCbl) to methylmalonyl-CoA mutase (MCM), the only AdoCbl-dependen

94 tion of 5'-deoxyadenosyl cobalamin-dependent methylmalonyl-CoA mutase (MCM).

95 so serves as an escort, delivering AdoCbl to methylmalonyl-CoA mutase (MCM).

96 Methylmalonyl-CoA mutase (MMCM) is an enzyme that utiliz

97 Our AAV vector was designed to insert a methylmalonyl-CoA mutase (MMUT) transgene into the 3' en

98 In these cells, the B(12)-dependent enzyme, methylmalonyl-CoA mutase (MMUT), plays a central role in

99 delivery and repair of B(12)-dependent human methylmalonyl-CoA mutase (MMUT).

100 oxidation-like pathways as well as inhibited methylmalonyl-CoA mutase (MUT) at lower doses.

101 L-Methylmalonyl-CoA mutase (MUT) is an adenosylcobalamin (

102 f metabolism caused by defective activity of methylmalonyl-CoA mutase (MUT) that exhibits multiorgan

103 ed by deficiency of the mitochondrial enzyme methylmalonyl-CoA mutase (MUT), is often complicated by

104 aciduria (MMAuria), caused by deficiency of methylmalonyl-CoA mutase (MUT), usually presents in the

105 inhibitor of the mitochondrial B12-dependent methylmalonyl-CoA mutase (MUT).

106 Methylmalonyl-CoA mutase accelerates the rate of Co-C bo

107 We found that nitric oxide (NO) inhibits methylmalonyl-CoA mutase activity in rodent cell extract

108 r inhibiting cellular NO synthesis increased methylmalonyl-CoA mutase activity when measured subseque

109 Methylobacterium extorquens, which supports methylmalonyl-CoA mutase activity, serves dual functions

110 nt activity of propionyl-CoA carboxylase and methylmalonyl-CoA mutase and are life-threatening condit

111 In the presence of methylmalonyl-CoA mutase and ATP, AdoCbl is transferred

112 nction of two crucial enzymes, mitochondrial methylmalonyl-CoA mutase and cytosolic methionine syntha

113 cluding adenosylcobalamin (AdoCbl)-dependent methylmalonyl-CoA mutase and hydrogenase, and thus have

114 In contrast, trans ligand effects in methylmalonyl-CoA mutase and indeed the significance of

115 ich catalyze carbon skeleton rearrangements, methylmalonyl-CoA mutase and isobutyryl-CoA mutase (ICM)

116 However, both methylmalonyl-CoA mutase and isobutyryl-CoA mutase, whic

117 The dissociation constant for binding of methylmalonyl-CoA mutase and MeaB ranges from 34 +/- 4 t

118 cs of interaction between the radical enzyme methylmalonyl-CoA mutase and MeaB, which are discussed.

119 impaired activity of the downstream enzymes, methylmalonyl-CoA mutase and methionine synthase.

120 on the kinetics of the reaction catalyzed by methylmalonyl-CoA mutase and on the thermodynamics of co

121 is to create the H610A and H610N variants of methylmalonyl-CoA mutase and report that both mutations

122 demonstrated that MeaB forms a complex with methylmalonyl-CoA mutase and stimulates in vitro mutase

123 Thus, NO inhibition of methylmalonyl-CoA mutase appeared to be from the reactio

124 ability of the double mutant (Y89F/R207Q) of methylmalonyl-CoA mutase as well as of the single mutant

125 Methylmalonyl-CoA mutase belongs to the class of adenosy

126 The inhibition of methylmalonyl-CoA mutase by NO was likely of physiologic

127 Methylmalonyl-CoA mutase catalyzes the adenosylcobalamin

128 Adenosylcobalamin-dependent methylmalonyl-CoA mutase catalyzes the interconversion o

129 Methylmalonyl-CoA mutase catalyzes the isomerization of

130 Methylmalonyl-CoA mutase catalyzes the isomerization of

131 el with samples from various mouse models of methylmalonyl-CoA mutase deficiency.

132 he hypothesis that MeaB functions to protect methylmalonyl-CoA mutase from irreversible inactivation.

133 MeaB and methylmalonyl-CoA mutase from M. extorquens were cloned

134 CoA, we inferred that conserved neighbors of methylmalonyl-CoA mutase genes and their human homologue

135 at were frequently arranged with prokaryotic methylmalonyl-CoA mutase genes, and that were of unknown

136 cobalamin-dependent methionine synthase and methylmalonyl-CoA mutase have revealed a striking confor

137 X-ray crystal structures of methylmalonyl-CoA mutase in complexes with substrate met

138 usly for the related Cbl-dependent isomerase methylmalonyl-CoA mutase indicate that a common mechanis

139 Methylmalonyl-CoA mutase is a key enzyme in intermediary

140 Methylmalonyl-CoA mutase is a member of the family of co

141 Methylmalonyl-CoA mutase is an 5'-adenosylcobalamin (Ado

142 Methylmalonyl-CoA mutase is an adenosylcobalamin (AdoCbl

143 Methylmalonyl-CoA mutase is an adenosylcobalamin-depende

144 yadenosylcobalamin by adenosyltransferase to methylmalonyl-CoA mutase is gated by a small G protein,

145 This study shows that methylmalonyl-CoA mutase is induced by several stresses,

146 alonyl-CoA supplied in vivo by the AtoAD and methylmalonyl-CoA mutase pathways, respectively, to prod

147 m under all conditions tested, and (iii) the methylmalonyl-CoA mutase reaction is reversible, but its

148 This portion of the methylmalonyl-CoA mutase sequence can be aligned with re

149 ace of the protein where its partner protein methylmalonyl-CoA mutase should bind.

150 m a primary CH(3)- group in AdoCbl-dependent methylmalonyl-CoA mutase shows the enzymic and enzyme-fr

151 ism is demonstrated by a patient mutation in methylmalonyl-CoA mutase that does not impair the activi

152 The alignments allow the mutations of human methylmalonyl-CoA mutase to be mapped onto the structure

153 mutase and a recently characterized archaeal methylmalonyl-CoA mutase, allowed demonstration of its r

154 ction of the radical B(12)-dependent enzyme, methylmalonyl-CoA mutase, although its precise role is n

155 enosylcobalamin (AdoCbl) to AdoCbl-dependent methylmalonyl-CoA mutase, an essential metabolic enzyme.

156 We show that methylmalonyl-CoA mutase, an R-specific crotonase, isobu

157 sential cofactor for methionine synthase and methylmalonyl-CoA mutase, but it must first undergo chem

158 ation of the enzymes methionine synthase and methylmalonyl-CoA mutase, disrupting gene expression and

159 adenosylcobalamin (AdoCbl)-dependent enzyme, methylmalonyl-CoA mutase, has been studied.

160 he essential enzymes methionine synthase and methylmalonyl-CoA mutase, respectively.

161 rone that escorts AdoCbl, transferring it to methylmalonyl-CoA mutase, which is important in propiona

162 tion of Co-carbon bond homolysis rate in the methylmalonyl-CoA mutase-catalyzed reaction has been eva

163 ct a qualitative free energy profile for the methylmalonyl-CoA mutase-catalyzed reaction.

164 ion of the active site residue, R207, in the methylmalonyl-CoA mutase-catalyzed reaction.

165 M3 and M2 labeled, reflecting reversal of S-methylmalonyl-CoA mutase.

166 ted with the homolysis reaction catalyzed by methylmalonyl-CoA mutase.

167 2-dependent enzymes, methionine synthase and methylmalonyl-CoA mutase.

168 cofactor required by methionine synthase and methylmalonyl-CoA mutase.

169 be a significant contributor to catalysis by methylmalonyl-CoA mutase.

170 ect residues in the C-terminal region of the methylmalonyl-CoA mutase.

171 um extorquens MeaB, which is a chaperone for methylmalonyl-CoA mutase.

172 dent target enzymes, methionine synthase and methylmalonyl-CoA mutase.

173 rotein interaction with its partner protein, methylmalonyl-CoA mutase.

174 n and assembly of the B(12)-dependent enzyme methylmalonyl-CoA mutase.

175 eaction catalyzed by the radical B12 enzyme, methylmalonyl-CoA mutase.

176 hich is stimulated approximately 100-fold by methylmalonyl-CoA mutase.

177 product Co2+ Cbl) is modulated by the enzyme methylmalonyl-CoA mutase.

178 osylcobalamin but due to an inactive form of methylmalonyl-CoA mutase.

179 e of the better characterized and homologous methylmalonyl-CoA mutase/G-protein chaperone system.

180 rward direction by reducing the ratio of apo-methylmalonyl-CoA mutase/holo-ATR required for delivery

181 thesis pathway and the vitamin B12-dependent methylmalonyl-CoA-mutase MutAB.

182 sets showed cystathionine beta synthase and methylmalonyl-CoA-mutase to be common to 3 out of 4 data

183 rk, to investigate the initial stages of the methylmalonyl-CoA-mutase-catalyzed reaction.

184 four-gene operon that encodes homologues of methylmalonyl CoA mutases (Sbm) and acyl CoA transferase

185 Because methylmalonyl-CoA mutases are involved in the metabolism

186 dicted gene product showed 35% identity with methylmalonyl-CoA mutases from various sources.

187 oop GTPase and are currently misannotated as methylmalonyl-CoA mutases.

188 which transfers the methylmalonyl moiety of methylmalonyl-CoA onto the phosphopantetheine arm of the

189 g only propionyl-CoA, and not malonyl-CoA, 2-methylmalonyl-CoA or acetyl-CoA, as the starter unit of

190 ive in MeaB and in the synthesis of either R-methylmalonyl-CoA or adenosylcobalamin indicates that Me

191 Subsequent binding of methylmalonyl-CoA (or CoA) promotes cob(II)alamin off-lo

192 the KS domains of MAS showed selectivity for methylmalonyl-CoA over malonyl-CoA.

193 ic acid N-acetylcysteamine thioester (2) and methylmalonyl-CoA plus NADPH result in formation of a re

194 valine degradation, implicated in providing methylmalonyl-CoA precursors for many polyketide biosynt

195 aA gene product is significantly involved in methylmalonyl-CoA production in S. cinnamonensis and tha

196 In this report, we identify the human DL-methylmalonyl-CoA racemase gene by analyzing prokaryotic

197 ble only at low propionyl-CoA flux, (ii) the methylmalonyl-CoA racemase reaction keeps the methylmalo

198 H0272 and its human homologue both encode DL-methylmalonyl-CoA racemases.

199 vides the structural basis for engineering a methylmalonyl-CoA reductase applied for biotechnical pol

200 These results show methylmalonyl-CoA selectivity for the AT and KS domains

201 action by orienting the carboxylate group of methylmalonyl CoA so that it is orthogonal to the plane

202 placing the AT domain of this protein with a methylmalonyl-CoA specific AT domain from module 6 of th

203 The methylmalonyl coenzyme A (methylmalonyl-CoA)-specific acyltransferase (AT) domains

204 When AT8 was replaced with methylmalonyl-CoA-specific AT domains, the strains produ

205 This led to engineering of the methylmalonyl-CoA specificity of both modules and invers

206 All 12 CoA's (CoASH, HMG CoA, methylmalonyl CoA, succinyl CoA, methylcrotonyl CoA, iso

207 ynthases that selectively use malonyl-CoA or methylmalonyl-CoA suggested that the acyltransferase (AT

208 lyketide synthase (PKS) used butyryl-CoA and methylmalonyl-CoA supplied in vivo by the AtoAD and meth

209 RpPat failed to acetylate the methylmalonyl-CoA synthetase of this bacterium (hereafte

210 confer to synthases that normally do not use methylmalonyl-CoA the ability to incorporate methylmalon

211 propionyl-CoA as its substrate and produces methylmalonyl-CoA, the substrate for the biosyntheses of

212 In the presence of [CD3]methylmalonyl-CoA, this rate decreases to 28 +/- 2 s(-1)

213 thase (PKS) that catalyzes the conversion of methylmalonyl-CoA to narbonolide and 10-deoxymethynolide

214 nthesis by catalyzing the decarboxylation of methylmalonyl-CoA to produce propionyl-CoA.

215 alyzes the transfer of a carboxyl group from methylmalonyl-CoA to pyruvate to form propionyl-CoA and

216 lyzing the transfer of a carboxyl group from methylmalonyl-CoA to pyruvate to form propionyl-CoA and

217 lation reactions, transferring CO(2)(-) from methylmalonyl-CoA to pyruvate to yield propionyl-CoA and

218 lation reactions, transferring CO(2)(-) from methylmalonyl-CoA to pyruvate, yielding propionyl-CoA an

219 product radical during the rearrangement of methylmalonyl-CoA to succinyl-CoA is unknown.

220 yl-CoA mutase catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA that uses reactive rad

221 mutase (MCM) catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA using 5'-deoxyadenosyl

222 somerases and catalyzes the rearrangement of methylmalonyl-CoA to succinyl-CoA.

223 t enzyme that catalyzes the rearrangement of methylmalonyl-CoA to succinyl-CoA.

224 t enzyme that catalyzes the rearrangement of methylmalonyl-CoA to succinyl-CoA.

225 rases and catalyzes the 1,2-rearrangement of methylmalonyl-CoA to succinyl-CoA.

226 zyme that catalyzes the 1,2 rearrangement of methylmalonyl-CoA to succinyl-CoA.

227 enzyme that catalyzes the isomerization of L-methylmalonyl-CoA to succinyl-CoA.

228 yl-CoA mutase catalyzes the isomerization of methylmalonyl-CoA to succinyl-CoA.

229 sylcobalamin-dependent rearrangement of (2R)-methylmalonyl-CoA to succinyl-CoA.

230 ompounds because of the inability to convert methylmalonyl-CoA to succinyl-CoA.

231 l) cofactor to catalyze the rearrangement of methylmalonyl-CoA to succinyl-CoA.

232 EpoC transfers the methylmalonyl moiety from methylmalonyl-CoA to the holo HS-acyl carrier protein (A

233 t chimeric protein converted diketide 1 with methylmalonyl-CoA to triketide ketolactone 6 with improv

234 nthesis can be primed via decarboxylation of methylmalonyl-CoA; under these conditions the overall k(

235 ation of the n-C12 acyl primer mainly by one methylmalonyl-CoA unit was catalyzed by an E. coli fatty

236 ns of AT4 believed to confer specificity for methylmalonyl-CoA were mutated into the sequence seen in

237 SMAS utilizes methylmalonyl-CoA with C12 to C20 acyl-CoA as primers an

238 hed that the decarboxylative condensation of methylmalonyl-CoA with S-propionyl-N-acetylcysteamine ca