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1 se caused by a deficiency of the enzyme beta-mannosidase.
2 lternate pathway comprising a distinct alpha-mannosidase.
3 ral and mechanistic dissection of endo-alpha-mannosidase.
4 de hydrolase (GH) family (GH164) of putative mannosidases.
5 in turn induces expression of secreted alpha-mannosidases.
6 base of the barrel similar to other Class 1 mannosidases.
7 )S5 conformational itinerary for GH125 alpha-mannosidases.
8 2 epitope is lost when gp120 is treated with mannosidases.
9 eviously unobserved structural-fold for beta-mannosidases.
10 tity) to class I animal and fungal alpha-1,2 mannosidases.
11 GH130 mannoside phosphorylases and beta-1,2-mannosidases.
12 ic GM inhibitors not affecting the lysosomal mannosidases.
13 ed glycans, including an abundance of acidic mannosidases.
14 r human lysosomal and Drosophila Golgi alpha-mannosidases.
15 tions processed for in situ hybridization of mannosidase 1, alpha (CA1), bcl-2-related ovarian killer
18 ed previously for the core-specific alpha1,6-mannosidase (acidic pH optimum, inhibition by swainsonin
22 ve subsequently demonstrated the presence of mannosidase activity in E. faecalis, which releases free
24 uences caused by the lack of cytosolic alpha-mannosidase activity in vivo by the generation of Man2c1
25 le continuous assay for measurement of alpha-mannosidase activity is described and demonstrated for a
26 vidence support a model in which neither the mannosidase activity nor catalytic domain is essential f
28 excellent substrate for the demonstration of mannosidase activity since it is a glycoprotein with a s
32 s of this enzyme indicated that it has alpha-mannosidase activity, however, we conclusively show that
33 1-deoxymannojirimycin, an inhibitor of alpha-mannosidase activity, without affecting the monomer popu
38 f a fusion between the first 13 exons in the mannosidase alpha class 2A member 1 gene (MAN2A1) and th
43 ining the open reading frame of endo-alpha-D-mannosidase, an enzyme involved in early N-linked oligos
44 nd mannose branching glycans, and alpha1-2,3 mannosidase, an enzyme that cleaves 1-2 and 1-3 mannopyr
45 ene organization with tomato endosperm beta -mannosidase and barley seed beta -glucosidase/ beta -man
47 ere constructed to localize active alpha-1,2-mannosidase and human beta-1,2-N-acetylglucosaminyltrans
49 the G protein with the exoglycosidase alpha-mannosidase and reduced after subsequent treatment with
50 f the antigen oligomannoside moiety by alpha-mannosidase and that CD1e is an accessory protein absolu
51 rly been used for identifying beta-(1 --> 4)-mannosidase and the derived Man(0) form has served in tu
52 talytic properties of the Sf9 class II alpha-mannosidase and to more clearly determine its relationsh
55 ries encoding catalytic domains of alpha-1,2-mannosidases and GnTI from mammals, insects, amphibians,
56 n), core-specific alpha1,6-mannosidase, beta-mannosidase, and cleavage at the reducing terminus by a
57 fluorescent protein-tagged soybean alpha-1,2 mannosidase, and correlated the findings to cytoskeletal
58 mmalian and yeast oligosaccharide-processing mannosidases, and the full-length coding region of the p
60 ymatic activities and joint actions of these mannosidases are required for this antiviral activity.
62 e cargo proteins, aminopeptidase I and alpha-mannosidase, are selectively transported from the cytopl
63 gh lvsB mutants inefficiently retained alpha-mannosidase, as well as two other lysosomal cysteine pro
66 mannosidase (LysMan), core-specific alpha1,6-mannosidase, beta-mannosidase, and cleavage at the reduc
68 .44 did not bind antigen treated with beta-D-mannosidase but did bind antigen treated with alpha-D-ma
69 nstrated that other mammalian class II alpha-mannosidases can participate in N-glycan processing.
78 ssembly and release of class II is linked to mannosidase-dependent ERAD targeting of the misfolded Ii
79 nce tags were identified for bovine alpha1,6-mannosidase, despite the identification of two sequence
80 med using recombinant Drosophila Golgi alpha-mannosidase (dGMII) has been shown to give the kinetic p
84 tion, we have identified three class I alpha-mannosidases, EDEM1, EDEM2, and ERManI, which play a cri
85 sidase, endo-(1-->4)-beta-D-xylanase, beta-D-mannosidase, endo-(1-->4)-beta-D-mannanase, alpha-D-xylo
87 ies of mammalian Class 1 processing alpha1,2-mannosidases (family 47 glycosidases) play critical role
88 1p (Htm1p-Pdi1p) acts as a folding-sensitive mannosidase for catalyzing this first committed step in
89 m temperature of LAM-spiked urine with alpha-mannosidase (for human TB), and LAM-spiked milk with com
90 ed activity-based protein profiling of alpha-mannosidases from both human cell lysate and mouse tissu
91 and the biologically relevant class II alpha-mannosidases from Drosophila melanogaster belonging to g
92 lts suggest that the chitobiase and alpha1,6-mannosidase function in tandem for mammalian lysosomal N
93 lying these traits as well as a single alpha-mannosidase gene directly associated with this tolerance
94 d the entire coding region of the human beta-mannosidase gene using a combination of cDNA library scr
95 '-flanking sequences for the bovine alpha1,6-mannosidase genes may lead to defective transcription si
96 uscle cell line C2, permanently expressing a mannosidase-green fluorescent protein (GFP) construct.
98 epitope-tagged full-length form of the human mannosidase homolog in normal rat kidney cells resulted
99 he full-length coding region of the putative mannosidase homolog was isolated by a combination of 5'-
100 he COOH-terminal luminal domain of the human mannosidase homolog, was expressed in COS cells, the fus
102 ibition of human endoplasmic reticulum alpha-mannosidase I (ER Man I) and mouse Golgi alpha-mannosida
103 , including endoplasmic reticulum (ER) alpha-mannosidase I (ERManI) and Golgi alpha-mannosidase IA (G
104 d how, modification by endoplasmic reticulum mannosidase I (ERManI) contributes to the preferential s
107 ene of Drosophila melanogaster encodes Golgi mannosidase I (MAS-1), and flies homozygous for small de
108 d by the sequential action of Golgi alpha1,2-mannosidase I (MIa,b,c), MGAT1, alpha1,2-mannosidase II
111 lycoprotein processing inhibitors that block mannosidase I and increase the amount of protein-bound M
112 me reactions using a combination of human ER mannosidase I and recombinant Golgi mannosidase IA indic
113 proteins as well as vesicle cargo molecules (mannosidase I and sialyltransferase-yellow fluorescent p
114 selective trimming of N-glycans by ER alpha-mannosidase I and subsequent recognition by the ER degra
115 ached to misfolded glycoproteins by ER alpha-mannosidase I and subsequent recognition by the ER degra
116 wild type and mutant forms of human ER alpha-mannosidase I as well as by structural analysis of a co-
117 erized by down-regulation of the Golgi alpha-mannosidase I coding gene MAN1A1, leading to elevation o
118 teolytically driven checkpoint control of ER mannosidase I contributes to the establishment of an equ
121 rent primary cells or in the presence of the mannosidase I inhibitor deoxymannojirimycin dramatically
123 ral serine kinase inhibition implied that ER mannosidase I is subjected to regulated proteolysis.
125 reshaping of the glycome by inhibiting alpha-mannosidase I resulted in significantly higher migratory
127 igosaccharides by endoplasmic reticulum (ER) mannosidase I targets misfolded glycoproteins for disloc
129 Herein the intracellular fate of human ER mannosidase I was monitored to determine whether a post-
131 MAN1B1 gene product MAN1B1, also known as ER mannosidase I, is to function within the ER similar to t
132 abidopsis (Arabidopsis thaliana) Golgi alpha-mannosidase I, Nicotiana tabacum beta1,2-N-acetylglucosa
133 haride modification by endoplasmic reticulum mannosidase I, the latter of which occurred as PI Z was
134 sly isolated for Saccharomyces cerevisiae ER mannosidase I, the oligosaccharide in the active site of
135 in which processing by endoplasmic reticulum mannosidase I, which attenuates the removal of glucose f
140 g five active eukaryotic proteins, including mannosidases I and II, N-acetylglucosaminyl transferases
142 alpha-mannosidase I (ERManI) and Golgi alpha-mannosidase IA (GMIA), are responsible for cleavage of t
144 nosidases, we have crystallized murine Golgi mannosidase IA (space group P2(1)2(1)2(1)), and the stru
145 human ER mannosidase I and recombinant Golgi mannosidase IA indicated that that these two enzymes are
147 nnose trimming enzyme drosophila Golgi alpha-mannosidase II (dGMII) complexed with the inhibitors man
151 aminyltransferase I, Arabidopsis Golgi alpha-mannosidase II (GMII), and Arabidopsis beta1,2-xylosyltr
154 GalT was compared with transfected rat alpha-mannosidase II (medial-Golgi, polyclonal antibody).
157 development consistent with increasing alpha-mannosidase II and core fucosyl-transferase enzyme activ
158 cDNA encoding a protein homologous to alpha-mannosidase II and designated it alpha-mannosidase IIx.
160 reen et al. now show that mice lacking alpha-mannosidase II develop an autoimmune disease similar to
164 nto small punctate structures at a time when mannosidase II is still largely localized to Golgi struc
166 ed oligosaccharides by endoplasmic reticulum mannosidase II partitions variant PI Z away from the con
167 on is temporally and spatially distinct from mannosidase II relocation and that FTCD provides a novel
169 onsisting of the first 117 residues of alpha-mannosidase II tagged with a fluorescent protein and a t
170 Swainsonine, an inhibitor of Golgi alpha-mannosidase II that causes abnormal N-glycosylation, str
171 taining pattern was similar to that of alpha-mannosidase II which is a known resident enzyme of the G
175 -GFP fusion colocalized with a Golgi marker, mannosidase II, and retained catalytic activity compared
176 Swainsonine, an inhibitor of Golgi alpha-mannosidase II, blocked beta1,6GlcNAc N-glycan expressio
177 tegral membrane Golgi proteins called GEARs (mannosidase II, GOS-28, GS15, GPP130, CASP, giantin, and
178 several Golgi and vesicle markers, including mannosidase II, p58, trans-Golgi network (TGN)38, and be
179 at mutation of a single gene, encoding alpha-mannosidase II, which regulates the hybrid to complex br
194 perties, we designated this enzyme Sf9 alpha-mannosidase III and concluded that it probably provides
197 disruption of Man2a2, a gene encoding alpha-mannosidase IIx (MX), an enzyme that forms intermediate
198 coexpressed with alpha-mannosidase II, alpha-mannosidase IIx colocalizes with alpha-mannosidase II in
199 in A fusion of the catalytic domain of alpha-mannosidase IIx hydrolyzes a synthetic substrate, 4-umbe
201 e, we show by immunocytochemistry that alpha-mannosidase IIx resides in the Golgi in HeLa cells.
202 ese hamster ovary cells overexpressing alpha-mannosidase IIx show a reduction of M(6)Gn(2) and an acc
204 ly, ER mannosidase I/Man1b1, the first alpha-mannosidase implicated in this conventional N-glycan-med
205 d with kifunensine, an inhibitor of alpha1,2-mannosidase in the ER, indicating that degradation of AT
206 analysis demonstrates that BtMan2A is a beta-mannosidase in which substrate binding energy is provide
208 pha- and beta-galactosidase, alpha- and beta-mannosidase) in an assay that measured the rate of hydro
209 e glycoside hydrolase family 47 (GH47) alpha-mannosidases, including endoplasmic reticulum (ER) alpha
210 m in which Golgi-localized MAN1B1 can play a mannosidase-independent gatekeeper role in the proteosta
212 al content of the beta subunit was less with mannosidase inhibition compared with that found in the N
215 hibitor lactacystin, and in combination with mannosidase inhibition, revealed that the removal of man
216 Complexes with the established endo-alpha-mannosidase inhibitor alpha-Glc-1,3-deoxymannonojirimyci
217 iated neutralization of JRFL produced with a mannosidase inhibitor further revealed that its neutrali
218 ctical synthesis of the potent class I alpha-mannosidase inhibitor kifunensine (1) beginning from the
219 hen Env was expressed in the presence of the mannosidase inhibitor kifunensine to force retention of
221 a CHO cell line in the presence of an alpha-mannosidase inhibitor kifunensine, and an endoglycosidas
222 pe KOR1 in the presence of the class I alpha-mannosidase inhibitor kifunensine, which abolished the c
223 ng several concentrations of the known alpha-mannosidase inhibitor swainsonine are also presented, de
224 reatment of zebrafish embryos with the alpha-mannosidase inhibitor swainsonine resulted in the accumu
226 er of alpha-mannosides, and the potential of mannosidase inhibitors as cellular probes and therapeuti
227 Compounds 15 and 16 were specific alpha-mannosidase inhibitors, and 24 and 26 were potent and se
228 se inhibitor, castanospermine (CST), and two mannosidase inhibitors, kifunensine (KIF) and deoxymanno
230 substrate interactions within the family 47 mannosidases involved in glycan maturation and ER-associ
231 f glycosidases including the Jack Bean alpha-mannosidase (JBalphaMan) and the biologically relevant c
234 the majority of strains transformed with the mannosidase/leader library displayed only modest in vivo
235 clinically and pathologically, tissue alpha-mannosidase levels were assayed, and in many studies, th
237 with kifunensine or disruption of the EDEM1 mannosidase-like domain by mutation had no effect on EDE
238 EDEM1 binds nonnative proteins and uses its mannosidase-like domain to target aberrant proteins to t
239 1 associates through a region outside of its mannosidase-like domain with the nonglycosylated protein
240 d upregulates ER degradation-enhancing alpha-mannosidase-like protein (EDEM) and ER chaperones, thus
241 mes predicted ER degradation-enhancing alpha-mannosidase-like protein and Mns1 orthologs, respectivel
242 nition by the ER degradation-enhancing alpha-mannosidase-like protein family of lectins, both members
243 nition by the ER degradation-enhancing alpha-mannosidase-like protein family of lectins, both members
244 lasmic reticulum degradation-enhancing alpha-mannosidase-like protein mRNA levels were inversely rela
245 tion of EDEM (ER degradation-enhancing alpha-mannosidase-like protein) also suppressed the degradatio
247 et gene EDEM (ER degradation-enhancing alpha-mannosidase-like protein, a protein degradation factor)
248 luding ERdj4, ER degradation-enhancing alpha-mannosidase-like protein, and p58(IPK), or expression of
249 through upregulation of ERAD-enhancing alpha-mannosidase-like proteins (EDEMs) protected against chro
250 atively, an alpha-1,2-mannosidase (Mns1) and mannosidase-like proteins (ER degradation-enhancing alph
251 ike proteins (ER degradation-enhancing alpha-mannosidase-like proteins 1, 2, and 3) are part of a pro
253 ncluding a broad specificity lysosomal alpha-mannosidase (LysMan), core-specific alpha1,6-mannosidase
254 ycan processing gene arrays identified alpha-mannosidases (MAN1A2 and MAN1C1) as targets for down-reg
255 (Nicotiana tabacum) plants of a human alpha-mannosidase, MAN2B1, which is a lysosomal enzyme involve
257 to one of the target genes, lysosomal beta A mannosidase (MANBA), we observed that genetic variants a
259 glycohydrolase family 38, namely Golgi alpha-mannosidase ManIIb (GM) and lysosomal alpha-mannosidase
262 e role of Arabidopsis thaliana class I alpha-mannosidases (MNS1 to MNS5) in glycan-dependent ERAD.
263 f the beta-1,2-xylose, followed by the alpha-mannosidase NixJ (GH125), which removes the alpha-1,6-ma
264 emoval of the alpha-1,3-mannose by the alpha-mannosidase NixK (GH92) is a prerequisite for the subseq
265 lines processed and targeted lysosomal alpha-mannosidase normally, indicating the lack of a significa
266 anavalin A as well as the enzymes alpha1-2,3 mannosidase or beta1-4 galactosidase to provide structur
267 se but did bind antigen treated with alpha-D-mannosidase, other alpha- or beta-glycosidases, or a pan
268 ine-linked oligosaccharides by a slow-acting mannosidase partitions the misfolded monomer into the pr
270 ervation that this motif is invariant in GH2 mannosidases points to a generic role for these residues
271 we determine that most glucosidases and beta-mannosidases preferentially bind their substrates in the
272 ides in the ER lumen, followed by ENGase and mannosidase processing in the cytosol and lysosomes.
274 ycoprotein as the substrate demonstrate that mannosidase production within the viridans group strepto
276 us for upper-lower lobe ratio near the alpha-mannosidase-related gene MAN2B1 (rs10411619; P = 1.1 x 1
277 frican Americans, a locus near a third alpha-mannosidase-related gene, MAN1C1 (rs12130495; P = 9.9 x
278 ent of the catalytic domain of class I alpha-mannosidases reveals four well-supported phylogenetic gr
279 he reaction coordinate of an inverting alpha-mannosidase show how the enzyme distorts the substrate a
280 ence, such as the neuraminidase NanA and the mannosidase SpGH92, we anticipate that the alpha-fucosid
281 o be less potent inhibitors of Class I alpha-mannosidases than kifuensine itself, the bis(hydroxymeth
282 length cDNA clone encoding a human alpha1, 2-mannosidase that catalyzes the first mannose trimming st
283 that Htm1p-Pdi1p is a glycoprotein-specific mannosidase that preferentially targets nonnative glycop
285 phosphate binding residues, are indeed beta-mannosidases that hydrolyze beta-1,2-mannosidic linkages
286 e found that it is a trimeric retaining beta-mannosidase, that is susceptible to several known mannos
287 tions of alpha-(1 --> 3) and alpha-(1 --> 6)-mannosidases, to the Man(1) form via Man(4), Man(3), and
291 asis for substrate recognition among Class 1 mannosidases, we have crystallized murine Golgi mannosid
293 e efficiency of targeting of lysosomal alpha-mannosidase were normal, although lvsB mutants inefficie
295 eriments, Rab7 T22N cells oversecreted alpha-mannosidase, whereas Rab7 WT cells retained this hydrola
296 (GFP) fusion protein co-localized with alpha-mannosidase, which indicated that the fusion protein loc
297 multiple enzymatic digestion steps including mannosidase with activity toward specific Man(alpha 1,3)
298 ct (Sf9) cell cDNA encoding a class II alpha-mannosidase with amino acid sequence and biochemical sim
299 ovel human glycosylhydrolase family 38 alpha-mannosidase with catalytic characteristics similar to th
300 city studies comparing the novel human alpha-mannosidase with human LysMan revealed that the former e