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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

26 2S,3R)-2-methyl-3-hydroxypentanoyl-SNAC (5), methylmalonyl-CoA, and NADPH with the recombinant [KS6][

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

60 0-kDa protein inhibited the incorporation of methylmalonyl-CoA into fatty acids by SMAS.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

108 Methylmalonyl-CoA mutase belongs to the class of adenosy

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

110 Methylmalonyl-CoA mutase catalyzes the adenosylcobalamin

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

112 Methylmalonyl-CoA mutase catalyzes the isomerization of

113 Methylmalonyl-CoA mutase catalyzes the isomerization of

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

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

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

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

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

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

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

121 Methylmalonyl-CoA mutase is a key enzyme in intermediary

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

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

124 Methylmalonyl-CoA mutase is an adenosylcobalamin (AdoCbl

125 Methylmalonyl-CoA mutase is an adenosylcobalamin-depende

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

143 2-dependent enzymes, methionine synthase and methylmalonyl-CoA mutase.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

162 Because methylmalonyl-CoA mutases are involved in the metabolism

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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