ライフサイエンスコーパス: IMPDH

1 IMPDH activity results from expression of two isoforms.

2 IMPDH catalyzes the conversion of IMP to XMP via a coval

3 IMPDH catalyzes the first dedicated step of GTP biosynth

4 IMPDH catalyzes the oxidation of IMP to XMP with the con

5 IMPDH catalyzes the oxidation of IMP to XMP with the con

6 IMPDH has an evolutionary conserved CBS subdomain of unk

7 IMPDH inhibitors have broad clinical applications in can

8 IMPDH is a promising target for chemotherapy.

9 IMPDH is a target for antitumor, antiviral, and immunosu

10 IMPDH is a target for numerous chemotherapeutic agents.

11 h the Tritrichomonas foetus and human type 2 IMPDHs using tiazofurin and ADP, which bind in the nicot

12 In addition, IMPDH type I(-/-) HPRT(-/0) splenocytes showed reduced i

13 Several classes of drugs are known to affect IMPDH isoenzymes, including nucleotide and NAD analogs,

14 ding to the Bateman domain without affecting IMPDH catalytic activity.

15 icroM) and was almost equally potent against IMPDH type I and type II.

16 partic acid at codon 226 is conserved in all IMPDH genes, in all species examined, including bacteria

17 ar is whether polymerization directly alters IMPDH catalytic activity.

18 site of the NAD+ site is not conserved among IMPDHs and is, therefore, a likely candidate.

19 Thus, development of an IMPDH inhibitor with a novel structure and a different p

20 However, mice with an IMPDH II(+/-), HPRT(-/o) genotype demonstrate significan

21 the four inteins gp41-1, gp41-8, NrdJ-1, and IMPDH-1 were prepared as fusion constructs with model pr

22 we show that both IMPDH type 1 (IMPDH1) and IMPDH type 2 are associated with polyribosomes, suggesti

23 variants IMPDH I rs2278293 and rs2278294 and IMPDH II rs11706052.

24 IMPDH I variants rs2278293 and rs2278294 and IMPDH II variant rs11706052, whereas others have failed

25 However, mycophenolic acid, another IMPDH inhibitor, had no antiviral effect.

26 ree crystal structures of Bacillus anthracis IMPDH, in a phosphate ion-bound (termed "apo") form and

27 This cation was not found previously in apo IMPDH, IMPDH in complex with XMP, or covalently bound in

28 ture of at least two structural forms of apo-IMPDH.

29 This is the first example of a bacterial IMPDH in more than one state from the same organism.

30 Comparison of the structure of bacterial IMPDH with the known partial structures from eukaryotic

31 yogenes IMPDH are similar to other bacterial IMPDH enzymes.

32 ntribute to the design of specific bacterial IMPDH inhibitors.

33 Thus, the bacterial IMPDH-specific NAD(+)-binding mode helps to rationalize

34 Potent inhibitors of bacterial IMPDHs have been identified that bind in a structurally

35 e and compared with those of three bacterial IMPDHs from Campylobacter jejuni, Clostridium perfringen

36 leading to a novel and potent acridone-based IMPDH inhibitor 4m and its efficacy and GI tolerability

37 of its critical role in purine biosynthesis, IMPDH is a drug design target for anticancer, antiinfect

38 olic hydroxamic acid (9, MAHA) inhibits both IMPDH (Ki=30 nM) and HDAC (IC50=5.0 microM).

39 We conclude that both IMPDH and HPRT activities contribute to normal T-lymphoc

40 Here we show that both IMPDH type 1 (IMPDH1) and IMPDH type 2 are associated wi

41 region in the substrate-free B. burgdorferi IMPDH and XMP-bound Chinese hamster IMPDH show that loop

42 NA strand cosegregation is also regulated by IMPDH and confirm the original implicit precept that imm

43 nhibitors of HMG-CoA reductase, calcineurin, IMPDH, PDE4, PI-3 kinase, hsp90, and p38 MAPK, among oth

44 esting that the previous putative P. carinii IMPDH might not represent full length, functional enzyme

45 gth, catalytically active form of P. carinii IMPDH.

46 Pneumocystis carinii f. sp. carinii IMPDH mRNA (GeneBank Accession No: U42442) previously id

47 In mammalian cells, IMPDH filaments can associate into micron-length assembl

48 IRES mRNA through the inhibition of cellular IMPDH activity, and induced PKR and eIF2alpha phosphoryl

49 agents, we have expressed and characterized IMPDH from the pathogenic bacterium Streptococcus pyogen

50 s as well as in the previously characterized IMPDH from Tritrichomonas foetus ( TfIMPDH).

51 resent two structures of the Vibrio cholerae IMPDH in complex with IMP/NAD(+) and XMP/NAD(+).

52 d are 1.4 nM and 53 nM for human and E. coli IMPDH, respectively.

53 ely impairs the activity of Escherichia coli IMPDH, decreasing the value of k(cat) by 650-fold.

54 r of both human type II and Escherichia coli IMPDH.

55 esting that inhibition of IMP dehydrogenase (IMPDH) and reduction of intracellular GTP levels were es

56 IMP dehydrogenase (IMPDH) catalyzes the oxidation of IMP to XMP with conver

57 IMP dehydrogenase (IMPDH) catalyzes the oxidation of IMP to XMP with the co

58 IMP dehydrogenase (IMPDH) catalyzes the oxidation of IMP to XMP with the co

59 IMP dehydrogenase (IMPDH) catalyzes the oxidation of IMP to XMP with the co

60 IMP dehydrogenase (IMPDH) catalyzes the oxidation of inosine 5'-monophospha

61 IMP dehydrogenase (IMPDH) catalyzes the pivotal step in guanine nucleotide

62 IMP dehydrogenase (IMPDH) catalyzes the rate-limiting step in the de novo s

63 IMP dehydrogenase (IMPDH) catalyzes two very different chemical transformat

64 IMP dehydrogenase (IMPDH) is an essential enzyme that catalyzes the first s

65 IMP dehydrogenase (IMPDH) is the rate-limiting enzyme for de novo GMP synth

66 IMP dehydrogenase (IMPDH) is the rate-limiting enzyme in the de novo synthe

67 viously, we proposed that IMP dehydrogenase (IMPDH) was an essential factor for p53-dependent asymmet

68 domain (CBS subdomain) of IMP dehydrogenase (IMPDH), a rate-limiting enzyme of the de novo GMP biosyn

69 and a potent inhibitor of IMP dehydrogenase (IMPDH).

70 id (MPA), an inhibitor of IMP-dehydrogenase (IMPDH), is used worldwide in transplantation.

71 n of inosine-5'-monophosphate dehydrogenase (IMPDH) activity, the target enzyme of the active moiety

72 and inosine 5'-monophosphate dehydrogenase (IMPDH) are purine metabolic enzymes that function mainta

73 Inosine 5'-monophosphate dehydrogenase (IMPDH) catalyses the rate-limiting step in guanine nucle

74 Inosine 5'-monophosphate dehydrogenase (IMPDH) catalyzes the conversion of IMP to XMP with the r

75 Inosine 5'-monophosphate dehydrogenase (IMPDH) catalyzes the first unique step of the GMP branch

76 Inosine-5'-monophosphate dehydrogenase (IMPDH) catalyzes the K+-dependent reaction IMP + NAD + H

77 Inosine 5'-monophosphate dehydrogenase (IMPDH) catalyzes the oxidation of IMP to XMP via the cov

78 Inosine 5'-monophosphate dehydrogenase (IMPDH) catalyzes the oxidation of inosine 5-monophosphat

79 Inosine monophosphate dehydrogenase (IMPDH) catalyzes the rate-limiting step in GMP biosynthe

80 Inosine monophosphate dehydrogenase (IMPDH) controls a key metabolic step in the regulation o

81 tion in inosine monophosphate dehydrogenase (IMPDH) enzyme activity and adverse effects caused by myc

82 s on inosine 5'-monophosphate dehydrogenase (IMPDH) for biosynthesis of guanine nucleotides and hence

83 y on inosine-5'-monophosphate dehydrogenase (IMPDH) for the biosynthesis of guanine nucleotides.

84 enzyme inosine monophosphate dehydrogenase (IMPDH) forms octamers that polymerize into helical chain

85 potent inosine monophosphate dehydrogenase (IMPDH) inhibitor but the antiviral mechanisms are less u

86 pecific inosine monophosphate dehydrogenase (IMPDH) inhibitor that results in depletion of intracellu

87 Inosine 5'-monophosphate dehydrogenase (IMPDH) is a rate-limiting enzyme in guanine nucleotide m

88 Inosine monophosphate dehydrogenase (IMPDH) is a rate-limiting enzyme required for the de nov

89 Inosine 5'-monophosphate dehydrogenase (IMPDH) is a rate-limiting enzyme that catalyzes the conv

90 Inosine monophosphate dehydrogenase (IMPDH) is a target for anticancer, antiviral, immunosupp

91 Inosine-5'-monophosphate dehydrogenase (IMPDH) is an attractive drug target for the control of p

92 Inosine-5'-monophosphate dehydrogenase (IMPDH) is an essential enzyme for nucleotide metabolism

93 enzyme inosine monophosphate dehydrogenase (IMPDH) is responsible for the rate-limiting step in guan

94 Inosine 5'-monophosphate dehydrogenase (IMPDH) is the critical, rate-limiting enzyme in the de n

95 Inosine 5'- monophosphate dehydrogenase (IMPDH) is the enzyme that catalyzes the oxidation of IMP

96 Inosine 5'-monophosphate dehydrogenase (IMPDH) is the rate-limiting enzyme in de novo guanine nu

97 Inosine 5'-monophosphate dehydrogenase (IMPDH) is the rate-limiting enzyme in de novo purine bio

98 Inosine 5'-monophosphate dehydrogenase (IMPDH) is the rate-limiting enzyme in the de novo synthe

99 s yeast inosine monophosphate dehydrogenase (IMPDH) mRNA synthesis by an unknown mechanism.

100 tion of inosine monophosphate dehydrogenase (IMPDH) potently inhibits DNA synthesis by arresting cell

101 The inosine monophosphate dehydrogenase (IMPDH) protein GuaB2 has been identified as a drugable t

102 s on inosine 5'-monophosphate dehydrogenase (IMPDH) to obtain guanine nucleotides, and inhibition of

103 s on inosine 5'-monophosphate dehydrogenase (IMPDH) to produce guanine nucleotides and is highly susc

104 itor of inosine monophosphate dehydrogenase (IMPDH) type II (Ki = 0.3 microM) as well as an inhibitor

105 man inosine- 5'-monophosphate dehydrogenase (IMPDH) type II, an enzyme catalyzing the rate-limiting s

106 Inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo synthesis of guanosi

107 nhibits inosine monophosphate dehydrogenase (IMPDH), a rate-limiting enzyme for the de novo synthesis

108 ed that Inosine Monophosphate Dehydrogenase (IMPDH), a rate-limiting enzyme in de novo guanine nucleo

109 Inosine monophosphate dehydrogenase (IMPDH), a rate-limiting enzyme in the de novo synthesis

110 tors of inosine monophosphate dehydrogenase (IMPDH), the corresponding fluorine-substituted methylene

111 vity of inosine monophosphate dehydrogenase (IMPDH), the rate-limiting enzyme required for the produc

112 tors of inosine monophosphate dehydrogenase (IMPDH).

113 s on inosine 5'-monophosphate dehydrogenase (IMPDH).

114 orms of inosine monophosphate dehydrogenase (IMPDH-1) is sufficient to cause endothelial cell cycle a

115 g for inosine 5-monophosphate-dehydrogenase (IMPDH).

116 micking inosine monophsophate dehydrogenase (IMPDH) inhibitors has prompted us to investigate novel m

117 malian inosine-monophosphate dehydrogenases (IMPDH); most microbial IMPDHs are not sensitive to MPA.

118 inhibitor of eukaryotic IMP dehydrogenases (IMPDHs).

119 Two separate isoenzymes, designated IMPDH types I and II, contribute to IMPDH activity.

120 Despite IMPDH is the target of drugs with antiviral, immunosuppr

121 lele, which encodes a catalytically disabled IMPDH(C305A) protein containing an intact Bateman domain

122 cription of PUR5, one of four genes encoding IMPDH-related enzymes.

123 size comparable to that of other eukaryotic IMPDH forms.

124 tion than reported previously for eukaryotic IMPDHs and other dehydrogenases, with the major change o

125 distinct pocket that is absent in eukaryotic IMPDHs.

126 dulates the catalytic activity of eukaryotic IMPDHs.

127 roduct of the enzyme, to indirectly evaluate IMPDH activity.

128 Lys310 and Glu431 of T. foetus IMPDH are replaced by Arg and Gln, respectively, in the

129 A comparison of T. foetus IMPDH with the Chinese hamster and Streptococcus pyogene

130 For T. foetus IMPDH, tiazofurin and ADP are extraordinarily synergisti

131 the protozoan parasite Tritrichomonas foetus IMPDH complexed with the inhibitor ribavirin monophospha

132 talytic core domain of Tritrichomonas foetus IMPDH in complex with IMP and beta-methylene-TAD at 2.2

133 y crystal structure of Tritrichomonas foetus IMPDH with mizoribine monophosphate (MZP) reveals a nove

134 D+ or NADH analogues, no structural data for IMPDH-bound NAD+ (or NADH) are available.

135 quence deleted from the chromosomal gene for IMPDH.

136 o mice deficient in HPRT or heterozygous for IMPDH type II.

137 etermined the complete kinetic mechanism for IMPDH from Tritrichomonas foetus using ligand binding, i

138 I is not a substrate for IMPDH.

139 Saccharomyces cerevisiae has four IMPDH genes called IMD1-IMD4.

140 Lymphocytes from IMPDH II(+/-) heterozygous mice are normal with respect

141 omplement the guaC (GMPR), but not the guaB (IMPDH), mutation in Escherichia coli.

142 gdorferi IMPDH and XMP-bound Chinese hamster IMPDH show that loop 6 follows a similar pattern of hing

143 ified previously only in the Chinese hamster IMPDH structure with covalently bound IMP.

144 imal medium, confirming that the protein has IMPDH activity.

145 polypeptides coassemble to form heteromeric IMPDH complexes, suggesting that they form mixed tetrame

146 ifferentially expressed genes included HPRT, IMPDH, PAICS, and GART, all of which were expressed at a

147 competitive inhibitor directed against human IMPDH.

148 in MPA affinity between T. foetus and human IMPDH.

149 ne transfer, and its host counterpart, human IMPDH type 2 (hIMPDH2).

150 Q277R/A462T is the first human IMPDH mutant with increased Ki for MPA and wild type act

151 rmined a minimal kinetic mechanism for human IMPDH type II using NAD analogs, isotope effects, hydrid

152 contains two residues that differ from human IMPDH.

153 ication of low nanomolar inhibitors of human IMPDH and more importantly the first potent inhibitor of

154 r range and >500-fold selectivity over human IMPDH (hIMPDH).

155 rovide evidence that expression of the human IMPDH type II gene is predominantly regulated by the nuc

156 xcellent selectivity >1000-fold versus human IMPDH type 2 and good stability in mouse liver microsome

157 sensitivity between the T. foetus and human IMPDHs derive from the residues in the MPA binding site.

158 DH bound to the active site of human type II IMPDH (IMPDH-h2).

159 n rapidly proliferating cells, human type II IMPDH is actively targeted for immunosuppressive, antica

160 ific inhibitors of human recombinant Type II IMPDH.

161 The catalytic mechanism of the human type-II IMPDH isozyme has been studied by measurement of the pH

162 d to the active site of human type II IMPDH (IMPDH-h2).

163 ation was not found previously in apo IMPDH, IMPDH in complex with XMP, or covalently bound inhibitor

164 induces a striking conformational change in IMPDH protein in intact cells, resulting in the formatio

165 acutely sensitive to even modest changes in IMPDH expression.

166 al biological function, a mouse deficient in IMPDH type I was generated by standard gene-targeting te

167 a tool for the detection of drug-inactivated IMPDH in the cells of patients receiving MPA therapy.

168 their inability to transcriptionally induce IMPDH.

169 gs that decrease GMP synthesis by inhibiting IMPDH have been shown to have antiproliferative as well

170 MPA inhibits IMPDH by binding in the nicotinamide half of the dinucle

171 ncreased sensitivity to a drug that inhibits IMPDH, 6-azauracil (6AU), by a mechanism that is poorly

172 afforded a SAHA analogue 14, which inhibits IMPDH (Ki=1.7 microM) and HDAC (IC50=0.06 microM).

173 found that MPA interacts with intracellular IMPDH in vivo to alter its mobility on SDS-polyacrylamid

174 Furthermore, C. parvum obtained its IMPDH gene by lateral transfer from an epsilon-proteobac

175 of this loop between beta6 and alpha6 links IMPDH to a family of beta/alpha barrel enzymes known to

176 ferences between the bacterial and mammalian IMPDH enzymes, making it an attractive target for antimi

177 lytic environment of bacterial and mammalian IMPDH enzymes.

178 re successful in the inhibition of mammalian IMPDH are far less effective against the microbial forms

179 ecies-specific inhibitor of IMPDH; mammalian IMPDHs are very sensitive to MPA, while the microbial en

180 cid (MPA) is a potent inhibitor of mammalian IMPDHs but a poor inhibitor of microbial IMPDHs.

181 fective and selective inhibitor of microbial IMPDH will be developed for use as a drug against multi-

182 ally target B. anthracis and other microbial IMPDH enzymes.

183 Microbial IMPDHs differ from mammalian enzymes in their lower affi

184 phate dehydrogenases (IMPDH); most microbial IMPDHs are not sensitive to MPA.

185 ian IMPDHs but a poor inhibitor of microbial IMPDHs.

186 omplexes in cell types that contain multiple IMPDH gene products.

187 monstrate that S. cerevisiae harbor multiple IMPDH enzymes with varying drug sensitivities and offer

188 are also involved when IMP binds to a mutant IMPDH in which the active site Cys is substituted with a

189 ease, and hydrolysis of E-XMP for the mutant IMPDHs.

190 The activities of IMPDH, adenylosuccinate synthetase and GMP reductase wer

191 show that in response to the application of IMPDH inhibitors such as 6AU, wild-type yeast strains in

192 al structures of four different complexes of IMPDH from the protozoan parasite Tritrichomonas foetus

193 ter understand the relative contributions of IMPDH types I and II and HPRT to normal biological funct

194 covalent adduct with the active-site Cys of IMPDH.

195 Thus, deletion of the Bateman domain of IMPDH derepresses the synthesis of AMP from IMP.

196 at in vivo deletion of the Bateman domain of IMPDH in Escherichia coli (guaB(DeltaCBS)) sensitizes th

197 We conclude that the Bateman domain of IMPDH is a negative trans-regulator of adenylate nucleot

198 de binding at the cofactor binding domain of IMPDH; however, they cannot participate in hydride trans

199 drug selectivity and catalytic efficiency of IMPDH isozymes.

200 To provide a basis for the evaluation of IMPDH inhibitors as antimicrobial agents, we have expres

201 ich the organism regulates the expression of IMPDH in response to environmental stresses.

202 values obtained from Molt-4 cell extracts of IMPDH.

203 is independent of the catalytic function of IMPDH in the de novo GMP biosynthesis.

204 es of protein with concomitant inhibition of IMPDH activity.

205 The inhibition of IMPDH by MPA is an example of this phenomenon.

206 offer an assay to monitor the inhibition of IMPDH in living cells.

207 Inhibition of IMPDH results in the depletion of guanine nucleotides, p

208 nsplant rejection based on its inhibition of IMPDH.

209 ellular guanosine pool through inhibition of IMPDH.

210 re importantly the first potent inhibitor of IMPDH from Mycobacterium tuberculosis (mtIMPDH).

211 d to be a 6-8 times less potent inhibitor of IMPDH than 5 (IC50 = 0.107 microM) and was almost equall

212 A prototypic uncompetitive inhibitor of IMPDH, mycophenolic acid (MPA), is the active form of my

213 cid (MPA) is a species-specific inhibitor of IMPDH; mammalian IMPDHs are very sensitive to MPA, while

214 Inhibitors of IMPDH activity selectively targeting the Type II isoform

215 t herein the synthesis of dual inhibitors of IMPDH and HDACs.

216 Inhibitors of IMPDH are also highly effective as immunosuppressive age

217 Since inhibitors of IMPDH are in clinical use as immunosuppressive agents, w

218 everal of the chemotherapeutic inhibitors of IMPDH are NAD+ or NADH analogues, no structural data for

219 of novel "allosteric-effector" inhibitors of IMPDH, to be used for the purpose of immunosuppression,

220 nary complex of the human type II isoform of IMPDH.

221 Two isoforms of IMPDH have been identified, one of which (type II) is si

222 we have delineated the kinetic mechanism of IMPDH from the pathogenic protozoan parasite Cryptospori

223 conformation for the catalytic mechanism of IMPDH-h2 are discussed.

224 embryonic lethality despite the presence of IMPDH type I and HPRT activities.

225 le-stranded nucleic acid binding property of IMPDH.

226 The role of IMPDH and interferon-stimulated genes (ISGs) was investi

227 rovide new tools for elucidating the role of IMPDH in C. parvum and may serve as potential therapeuti

228 We have determined the crystal structure of IMPDH from Borrelia burgdorferi, the bacterial spirochet

229 This is the first structure of IMPDH in the absence of substrate or cofactor where the

230 e- or substrate analogue-bound structures of IMPDH, suggestive of a conformational change.

231 We conclude that the CBS subdomain of IMPDH may coordinate the activities of the enzymes of pu

232 roscopy to investigate the ultrastructure of IMPDH macrostructures and live-cell imaging to follow cl

233 PA's antiviral activity partially depends on IMPDH but also involves stimulation of ISGs, providing a

234 hosphate dehydrogenase (IMP dehydrogenase or IMPDH) is a promising target for the development of new

235 Knockdown of PKR or IMPDH prevented RBV induced HCV IRES-GFP translation.

236 cell lines underscored the importance of p53-IMPDH-rGNP regulation for normal tissue cell kinetics, p

237 selective urea-based inhibitor of C. parvum IMPDH (CpIMPDH) identified by high-throughput screening.

238 ntified several parasite-selective C. parvum IMPDH (CpIMPDH) inhibitors by high-throughput screening.

239 perties of the NAD binding site of C. parvum IMPDH can be exploited to develop parasite-specific inhi

240 ribe the expression of recombinant C. parvum IMPDH in an Escherichia coli strain lacking the bacteria

241 Because C. parvum IMPDH is highly divergent from the host counterpart, sel

242 The pronounced resistance of C. parvum IMPDH to mycophenolic acid inhibition is in strong agree

243 otential of two known Cryptosporidium parvum IMPDH inhibitors was examined for the B. anthracis enzym

244 lobacter jejuni, and Clostridium perfringens IMPDHs.

245 effects of mycophenolic acid (MPA), a potent IMPDH inhibitor, on the cell cycle progression of activa

246 venting the regulatory terminator to produce IMPDH mRNA.

247 on adopted by several classes of prokaryotic IMPDH inhibitors.

248 Treatment of highly purified IMPDH with MPA also results in the formation of large ag

249 l and kinetic characteristics of S. pyogenes IMPDH are similar to other bacterial IMPDH enzymes.

250 S. pyogenes IMPDH is a tetramer with its four subunits related by a

251 ctive or inactive conformations, recombinant IMPDH filaments accommodate multiple states.

252 rized and non-assembled forms of recombinant IMPDH have comparable catalytic activity, substrate affi

253 is response does not result from the reduced IMPDH activity or starvation for guanylates.

254 The MPA binding site of resistant IMPDH from the parasite Tritrichomonas foetuscontains tw

255 evicompactum (Pb) contains two MPA-resistant IMPDHs, PbIMPDH-A and PbIMPDH-B, which are 17- and 10(3)

256 GTP also restores IMPDH activity.

257 ounds represent the first class of selective IMPDH Type II inhibitors which may serve as lead compoun

258 Here, we show that, unlike MPA-sensitive IMPDHs, formation of E-XMP* is rate-limiting for both Pb

259 tosis by mycophenolic acid (MPA), a specific IMPDH inhibitor, in interleukin-3 (IL-3)-dependent murin

260 pproach is applied to three protein systems: IMPDH, MAP kinase p38, and HIV-1 aspartyl protease.

261 nd pave the road to new approaches targeting IMPDHs.

262 ino acids shorter at the amino terminus than IMPDH from other species.

263 These results indicate that IMPDH inhibitors may be effective in modulating signal t

264 hinged rigid-body motion and indicates that IMPDH may be using loop 6 to bind and sequester substrat

265 We propose that IMPDH coordinates the translation of a set of mRNAs, per

266 and that there were differences between the IMPDH isoforms, IMPDH1 and IMPDH2.

267 (rs2278293) and G alleles (rs2278294) in the IMPDH I variants and carriage of the G allele (rs1170605

268 carriage of the G allele (rs11706052) in the IMPDH II variant did not increase the risk of rejection

269 The pKs of the acids observed in the IMPDH reaction likely also reflect ionization of the cys

270 rves as the base that activates water in the IMPDH reaction.

271 be the role of the Arg418-Tyr419 dyad in the IMPDH reaction.

272 ve as an analogue for an intermediate in the IMPDH reaction.

273 ins to mediate the catalytic activity of the IMPDH and GMPR provides a regulatory mechanism for balan

274 cient, Pol II initiates transcription of the IMPDH gene (IMD2) at TATA box-proximal "G" sites, produc

275 here are no other essential functions of the IMPDH homologs aside from IMP dehydrogenase activity.

276 The pH dependence of the IMPDH reaction shows bell-shaped profiles for kcat and t

277 bonding interactions in the chemistry of the IMPDH reaction than simply in nucleotide binding.

278 ure and solves the mechanistic puzzle of the IMPDH reaction.

279 lies in the NAD(H)-dependent segment of the IMPDH reaction.

280 ntrast to the >100-fold K+ activation of the IMPDH reaction.

281 xamined the consequences of knocking out the IMPDH type II enzyme by gene targeting in a mouse model.

282 These findings support the idea that the IMPDH isoforms are subject to distinct regulation and th

283 us evidence for an association between these IMPDH variants and renal allograft rejection and graft s

284 Computational studies of these IMPDH enzymes helped rationalize the observed structure-

285 Three IMPDH splicing variants were found and splicing preferen

286 Thus, IMPDH inhibitors have great potential as chemotherapeuti

287 g studies predict that the compounds bind to IMPDH in the IMP-binding site, although interactions wit

288 an antagonist to MPA by directly binding to IMPDH and reversing the conformational changes in the pr

289 Finally, GTP binds to IMPDH at physiologic concentrations, induces the formati

290 signated IMPDH types I and II, contribute to IMPDH activity.

291 ine nucleotides and is highly susceptible to IMPDH inhibition.

292 of NADH production is observed for wild-type IMPDH, no burst is observed for Asp338Ala.

293 en 2-(2)H-IMP is the substrate for wild-type IMPDH.

294 tudy DNA bank was genotyped for the variants IMPDH I rs2278293 and rs2278294 and IMPDH II rs11706052.

295 Bateman domain has no effect on the in vitro IMPDH activity.

296 an be deleted without impairing the in vitro IMPDH catalytic activity and is the site for mutations a

297 the foundation for clinical trials in which IMPDH inhibitors are added to imatinib in patients who h

298 With IMPDH being the rate-determining enzyme for guanine ribo

299 n of SAHA with groups known to interact with IMPDH afforded a SAHA analogue 14, which inhibits IMPDH

300 orphism and the risk of acute rejection with IMPDH I variants rs2278293 and rs2278294 and IMPDH II va