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71.
Manya H Sakai K Kobayashi K Taniguchi K Kawakita M Toda T Endo T 《Biochemical and biophysical research communications》2003,306(1):93-97
Muscle-eye-brain disease (MEB), an autosomal recessive disorder, is characterized by congenital muscular dystrophy, brain malformation, and ocular abnormalities. Previously, we found that MEB is caused by mutations in the gene encoding the protein O-linked mannose beta1,2-N-acetylglucosaminyltransferase 1 (POMGnT1), which is responsible for the formation of the GlcNAcbeta1-2Man linkage of O-mannosyl glycan. Although 13 mutations have been identified in patients with MEB, only the protein with the most frequently observed splicing site mutation has been studied. This protein was found to have no activity. Here, we expressed the remaining mutant POMGnT1s and found that none of them had any activity. These results clearly demonstrate that MEB is inherited as a loss-of-function of POMGnT1. 相似文献
72.
Hisano T Tsuge T Fukui T Iwata T Miki K Doi Y 《The Journal of biological chemistry》2003,278(1):617-624
The (R)-specific enoyl coenzyme A hydratase ((R)-hydratase) from Aeromonas caviae catalyzes the addition of a water molecule to trans-2-enoyl coenzyme A (CoA), with a chain-length of 4-6 carbons, to produce the corresponding (R)-3-hydroxyacyl-CoA. It forms a dimer of identical subunits with a molecular weight of about 14,000 and is involved in polyhydroxyalkanoate (PHA) biosynthesis. The crystal structure of the enzyme has been determined at 1.5-A resolution. The structure of the monomer consists of a five-stranded antiparallel beta-sheet and a central alpha-helix, folded into a so-called "hot dog" fold, with an overhanging segment. This overhang contains the conserved residues including the hydratase 2 motif residues. In dimeric form, two beta-sheets are associated to form an extended 10-stranded beta-sheet, and the overhangs obscure the putative active sites at the subunit interface. The active site is located deep within the substrate-binding tunnel, where Asp(31) and His(36) form a catalytic dyad. These residues are catalytically important as confirmed by site-directed mutagenesis and are possibly responsible for the activation of a water molecule and the protonation of a substrate molecule, respectively. Residues such as Leu(65) and Val(130) are situated at the bottom of the substrate-binding tunnel, defining the preference of the enzyme for the chain length of the substrate. These results provide target residues for protein engineering, which will enhance the significance of this enzyme in the production of novel PHA polymers. In addition, this study provides the first structural information of the (R)-hydratase family and may facilitate further functional studies for members of the family. 相似文献
73.
Glycoproteins in the soluble fraction and in the membrane fraction of various portions of brains and spinal cords, obtained from 9-week-old rats and 29-month-old rats, were comparatively analyzed by SDS-polyacrylamide gel electrophoresis and lectin staining. The glycoprotein patterns of each brain part showed marked differences by the age of donors. The most prominent evidence in the soluble fractions of white matter, basal ganglia, and spinal cord detected by WGA is that the glycoproteins with an apparent molecular weight of 123K and 115K have increased in the aged rats. In addition, the reactivity of 115K with Con A and PNA has also increased in the aged rats. On the other hand, reactivity of an apparent molecular weight of 115K with WGA has increased in the membrane fractions of white matter, basal ganglia, hippocampus, cerebellum, and spinal cord from the aged rats. In contrast, by MAM, which is specific for Sia2®3Gal linkage, an apparent molecular weight of 115K has been detected only in the membrane fraction of cerebellum and it has decreased in the aged rats. Reactivity of an apparent molecular weight of 133K and 125K in the membrane fractions of white matter and basal ganglia with LCA has decreased in the aged rats. In contrast, reactivity of the front band with LCA and AAL has increased and that of 130K with AAL has decreased in spinal cord from the aged rats, respectively. These results indicate that the glycosylation state of the protein in the brain changes during aging. 相似文献
74.
Marcy N Wilder Kazumasa Ikuta Muharijadi Atmomarsono Tamao Hatta Kosei Komuro 《Comparative biochemistry and physiology. Part A, Molecular & integrative physiology》1998,119(4):89
Osmotic and ionic regulatory ability were examined in the giant freshwater prawn, Macrobrachium rosenbergii in response to varying salinities. In freshwater, and under conditions of low salinity, hemolymph osmolality was maintained around 450 mOsm. Under high salinity, osmolality values increased in a time-wise manner until reaching levels of the surrounding rearing water. Changes in sodium concentration generally paralleled osmotic change, and potassium and magnesium concentrations increased upon exposure to extremely high salinity. In contrast, total calcium concentration was maintained at high levels regardless of salinity treatment. Examination of crystalline structure and ionic composition of the cuticle revealed that it was comprised principally of an α-chitin-like material, and calcite (calcium carbonate). Calcite accounted for 25% of total bulk weight in freshwater, while sodium, potassium and magnesium constituents combined comprised less than 2.5% of this total. Although sodium, potassium and magnesium contents increased nearly 2-fold in response to changing salinity, calcium levels remained relatively constant. 相似文献
75.
Microbial degradation of phenylacetic acid proceeds via the hybrid pathway that includes formation of a coenzyme A thioester, ring hydroxylation, non‐oxygenolytic ring opening, and β‐oxidation‐like reactions. A phenylacetic acid degradation protein PaaG is a member of the crotonase superfamily, and is a candidate non‐oxygenolytic ring‐opening enzyme. The crystal structure of PaaG from Thermus thermophilus HB8 was determined at a resolution of 1.85 Å. PaaG consists of three identical subunits related by local three‐fold symmetry. The monomer is comprised of a spiral and a helical domain with a fold characteristic of the crotonase superfamily. A putative active site residue, Asp136, is situated in an active site cavity and surrounded by several hydrophobic and hydrophilic residues. The active site cavity is sufficiently large to accommodate a ring substrate. Two conformations are observed for helix H2 located adjacent to the active site. Helix H2 is kinked at Asn81 in two subunits, whereas it is kinked at Leu77 in the other subunit, and the side chain of Tyr80 is closer to Asp136. This indicates that catalytic reaction of PaaG may proceed with large conformational changes at the active site. Asp136 is the only conserved polar residue in the active site. It is located at the same position as those of 4‐chlorobenzoyl‐CoA dehalogenase and peroxisomal Δ3,Δ2‐enoyl‐CoA isomerase, indicating that PaaG may undergo isomerization or a ring‐opening reaction via a Δ3,Δ2‐enoyl‐CoA isomerase‐like mechanism. Proteins 2009. © 2009 Wiley‐Liss, Inc. 相似文献
76.
Matsuo A Bellier JP Hisano T Aimi Y Yasuhara O Tooyama I Saito N Kimura H 《Neurochemistry international》2005,46(5):423-433
Choline acetyltransferase (ChAT), the synthesizing enzyme for acetylcholine, has been implicated to involve multiple isoforms of ChAT mRNA in several animals. Since these isoforms are mostly non-coding splice variants, only a homologous ChAT protein of about 68 kDa has been shown to be produced in vivo. Recent evidence indicates the existence of a protein coding splice variant of ChAT mRNA, which lacks exons 6-9 of the rat ChAT gene. The encoded protein was designated ChAT of a peripheral type (pChAT), because of its preferential expression in the peripheral nervous system as confirmed by Western blot and immunohistochemistry. However, functional significance of pChAT is unknown. To obtain a clue to this question, we examined a possible difference in intracellular trafficking between pChAT and the well-known ChAT of the common type (cChAT) using green fluorescent protein (GFP) in living human embryonic kidney cells. Confocal laser scanning microscopy revealed that pChAT-GFP was detectable in the cytoplasm but not in the nucleus, whereas cChAT-GFP was found in both cytoplasm and nucleus. Following treatment with leptomycin B, a nuclear export pathway inhibitor, pChAT-GFP became detectable in both cytoplasm and nucleus, indicating that pChAT can be translocated to the nucleus. In contrast, the leptomycin B treatment did not seem to affect the content of intranuclear cChAT-GFP. After incubation with protein kinase C inhibitors, enhanced accumulation of pChAT-GFP but not cChAT-GFP occurred in the nucleus. These results clearly indicate that pChAT varies from cChAT in intracellular transportation, probably reflecting the difference in physiological roles between pChAT and cChAT. 相似文献
77.
Kano H Kobayashi K Herrmann R Tachikawa M Manya H Nishino I Nonaka I Straub V Talim B Voit T Topaloglu H Endo T Yoshikawa H Toda T 《Biochemical and biophysical research communications》2002,291(5):1283-1286
Alpha-dystroglycan is a component of the dystrophin-glycoprotein-complex, which is the major mechanism of attachment between the cytoskeleton and the extracellular matrix. Muscle-eye-brain disease (MEB) is an autosomal recessive disorder characterized by congenital muscular dystrophy, ocular abnormalities and lissencephaly. We recently found that MEB is caused by mutations in the protein O-linked mannose beta1,2-N-acetylglucosaminyltransferase (POMGnT1) gene. POMGnT1 is a glycosylation enzyme that participates in the synthesis of O-mannosyl glycan, a modification that is rare in mammals but is known to be a laminin-binding ligand of alpha-dystroglycan. Here we report a selective deficiency of alpha-dystroglycan in MEB patients. This finding suggests that alpha-dystroglycan is a potential target of POMGnT1 and that altered glycosylation of alpha-dystroglycan may play a critical role in the pathomechanism of MEB and some forms of muscular dystrophy. 相似文献
78.
Yamaguchi K Ushijima H Hisano M Inoue Y Shimamura T Hirano T Müller WE 《Microbiology and immunology》2001,45(7):549-555
Induction of IL-2 production and increased expression of CD25 were observed in C57BL/10 mice after weekly treatment with gold sodium thiomalate (GST). LP-BM5 murine leukemia virus (MuLV) infected mice treated with GST survived longer, had less cervical lymph node swelling, lower spleen weight, and fewer abnormalities in the expression of the cell surface markers, CD4, CD8a and CD45R/B220 on spleen cells than those that were not treated with GST. Thus, GST treatment may be beneficial through a decrease in disease progression via IL-2 induction in MuLV infected mice. This may have application in human immunodeficiency virus-infected individuals. 相似文献
79.
Kojima S Hisano Y Miura K 《Biochemical and biophysical research communications》2001,281(5):1271-1276
Pleurotus ostreatus proteinase A inhibitor 1 (POIA1), which is composed of 76 residues without disulfide bridges, is a unique inhibitor in that it exhibits sequence similarity to the propeptides of subtilisins. In order to elucidate the inhibitory mechanism of POIA1, we constructed an expression system for a synthetic POIA1 gene. The wild-type POIA1 was found to inhibit subtilisin BPN' with an inhibitor constant (K(i)) of 3.2 x 10(-9) M, but exhibited a time-dependent decrease of inhibitory activity as a consequence of degradation by the protease, showing that the wild-type POIA1 was a temporary inhibitor when subtilisin BPN' was used as a target protease. Since POIA1 shows sequence similarity to the propeptide of subtilisin, which is known to inhibit the protease via its C-terminal region, the C-terminal six residues of POIA1 were replaced with those of the propeptide of subtilisin BPN'. The mutated POIA1 inhibited subtilisin BPN' with a K(i) value of 2.8 x 10(-11) M and did not exhibit time-dependent decrease of inhibitory activity, showing about 100-fold increases in binding affinity for, and resistance to, the protease. These results clearly indicate that the C-terminal region of POIA1 plays an important role in determining the inhibitory activity toward the protease, and that the increase in binding ability to the protease is closely related to resistance to proteolytic degradation. Therefore, the inhibitory properties of POIA1 can be altered by mutation of its C-terminal region. 相似文献
80.
Setsuji Hisano Hitoshi Kawano Yuzo Maki Prof. Dr. Shigeo Daikoku 《Cell and tissue research》1981,220(3):511-518
Summary In early postnatal rats, immunoreactive LHRH perikarya in the preoptic area were studied by light and electron microscopy. Synaptic junctions were found between the immunoreactive perikaryon or its process, and the immunonegative nerve fibers. The significance of these synapses is discussed in relation to possible mechanisms by which the activities of LHRH neurons are regulated. 相似文献