Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.1.53 (sialidase)
 2,694 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A deaminoneuraminosyl-glycohydrolase (KDNase), which catalyses the hydrolysis of alpha-ketosidic 2-keto-3-deoxy-D-glycero-D-galacto- nononic acid (or naturally occurring deaminated neuraminic acid; KDN) linkages in KDN-glycoconjugates, is required for their structural and functional studies since KDN residues are usually resistant to the action of known sialidases. A search for KDNase was initiated by examining various cells and tissues of rainbow trout because KDN-glycoconjugates were first found in this animal species. Tissue localization studies of KDNase activity showed it to be present in kidney, spleen and ovary. The highest KDNase activity was found in ovarian post-ovulatory follicles obtained from female fish at the time when the reproductive organ was undergoing natural effacement. Little if any activity was found in brain, heart, liver, muscle, mature eggs and testis. Developmentally, higher levels of KDNase were usually expressed 3-4 months before ovulation or spermiation. An exception to this was in the ovary (or ovarian follicles) where the most striking increase in KDNase occurred 1-2 months after the maturation of gamete cells. Enzyme extracts containing KDNase activity also contained sialidase activity. From the data based on a kinetic study using mixed substrates, both KDNase and sialidase activities were indicated to reside on a single enzyme protein. The KDN-sialidase displayed broad specificity, which could possibly limit its usefulness as a probe for KDN-glycoconjugates. Nevertheless, unlike sialidases, KDNase can selectively remove KDN residues, thus making it an important new reagent to identify KDN-glycoconjugates in vivo.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Identification, developmental expression and tissue distribution of deaminoneuraminate hydrolase (KDNase) activity in rainbow trout. 782 13

We have examined the tissues of several species of fish and found that the liver of the loach (Misgurnus fossilis) contains a novel sialidase capable of efficiently hydrolyzing 3-deoxy-D-glycero-D-galacto-2-nonulosonic acid (KDN) from the 4-methylumbelliferyl alpha-ketoside of KDN, KDN alpha 2-->3Gal beta 1-->4GlcCer and KDN alpha 2-->6 N-acetylgalactosaminitol as well as Neu5Ac from the 4-methylumbelliferyl alpha-ketoside of Neu5Ac and GM3. The pH optimum for this enzyme was determined to be 4.6, and the Km using the 4-methylumbelliferyl alpha-ketoside of KDN and 4-methylumbelliferyl alpha-ketoside of Neu5Ac as substrates were 0.07 and 0.12 mM, respectively. The enzyme was stable in the pH range of 4 to 5 but very unstable above pH 6. This is the first report of a sialidase capable of efficiently cleaving glycosidically linked KDN.
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PMID:A novel sialidase capable of cleaving 3-deoxy-D-glycero-D-galacto-2-nonulosonic acid (KDN). 816 Dec 11

We have found the coexistence of two different sialidases in the entrails of the starfish Asterina pectinifera: a regular sialidase (RS), which cleaves sialic acid from sialoglycoconjugates, and a KDN-sialidase (KS) which releases the sialic acid analogue KDN (2-keto-3-deoxy-D-glycero-d-galacto-nononic acid) from KDN-containing glycoconjugates that are resistant to RS. The 6700-fold purified KS and 1300-fold purified RS were prepared to study the properties of these two sialidases. KS and RS from Asterina starfish differ in several properties other than glycon specificity, including molecular mass, isoelectric point (pI) and susceptibility to competitive and non-competitive inhibitors. KS has a molecular mass of 31 kDa and a pI of 8.3 while RS has a molecular mass of 128 kDa and a pI of about 4.8. 2,3-dehydro-2-deoxy-N-acetylneuraminic acid (NeuAc2en), but not 2,3-dehydro-2-deoxy-KDN (KDN2en), is a potent competitive inhibitor of RS (Ki approximately 0.007 mM); however, both NeuAc2en and KDN2en are moderate inhibitors of KS (K1 approximately 0.04 mM). Hg2+ is a potent non-competitive inhibitor of RS but not of KS. KS and RS were examined for their ability to hydrolyse KDN- and NeuAc-containing glycoconjugates. KS hydrolyses 4-methyl-umbelliferyl-alpha-KDN (MU-KDN) 20 times faster than 4-methylumbelliferyl-alpha-NeuAc (MU-NeuAc), while RS hydrolyses MU-NeuAc 88 times faster than MU-KDN at the pH optimum of 4.0 KS effectively hydrolyses KDN-GM3 (where GM3 is NeuAc alpha 2 --> 3Gal beta 1 --> 4Glc beta 1-1' Cer, and Cer is ceramide), KDN alpha 2 --> 3lactose, KDN alpha 2 --> 6lactose, KDN alpha 2 --> 6N-acetylgalactosaminitol, KDN alpha 2 --> 6 (KDN alpha 2 --> 3)N-acetylgalactosaminitol and KDN alpha 2 --> 6(GlcNAc beta 1 --> 3) N-acetylgalactosaminitol. However, under the same conditions, these KDN-containing glycoconjugates are refractory to RS. Conversely, GM3, NeuAc alpha 2 --> 3lactose and NeuAc alpha 2 --> 6lactose are effectively hydrolysed by RS but not by KS.
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PMID:Two different sialidases, KDN-sialidase and regular sialidase in the starfish Asterina pectinifera. 864 42

Homopolymers of alpha 2,8-linked N-acetylneuraminic acid [poly(alpha 2,8-Neu5Ac)] of the neural cell adhesion molecule NCAM have been shown to be temporally expressed during lung development and represent a marker for small cell lung carcinoma. We report the presence of a further polysialic acid in lung that consists of oligo/polymers of alpha 2,8-linked deaminoneuraminic acid residues [poly (alpha 2,8-KDN)], as detected with a monoclonal antibody in conjunction with a specific sialidase. Although the various cell types forming the bronchi, alveolar septs, and blood vessels were positive for poly (alpha 2,8-KDN) by immunohistochemistry, this polysialic acid was found on a single 150-kDa glycoprotein by immunoblot analysis. The poly(alpha 2,8-KDN)-bearing glycoprotein was not related to an NCAM protein based on immunochemical criteria. The expression of the poly (alpha 2,8-KDN) was developmentally regulated as evidenced by its gradual disappearance in the rat lung parenchyma commencing 1 week after birth. In adult lung the blood vessel endothelia and the smooth muscle fibers of both blood vessels and bronchi were positive but not the bronchial and alveolar epithelium. The poly (alpha 2,8-KDN)-bearing 150-kDa glycoprotein became reexpressed in various histological types of lung carcinomas and cell lines derived from them and represents a new oncodevelopmental antigen in lung.
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PMID:Poly (alpha 2,8-deaminoneuraminic acid) is expressed in lung on a single 150-kDa glycoprotein and is an oncodevelopmental antigen. 879 42

The mechanism of hydrolysis of 4-methylumbelliferyl 3-deoxy-D-glycero-alpha-D-galacto-2-nonulopyranosidonic acid (KDN alpha 2MeUmb, 4) by KDN-sialidase isolated from the hepatopancreas of the oyster Crassostrea virginica has been monitored by 1H NMR spectroscopy. The results of these experiments reveal that KDN-sialidase catalyses the hydrolysis of the synthetic substrate KDN alpha 2MeUmb, with initial release of alpha-D-KDN. This is consistent with an overall mechanism for the hydrolysis which proceeds with retention of anomeric configuration. These results agree with earlier NMR studies of other N-acetylneuraminic acid-recognising sialidases from both viral and bacterial sources.
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PMID:A 1H NMR investigation of the hydrolysis of a synthetic substrate by KDN-sialidase from Crassostrea virginica. 898 Oct 83

Deaminoneuraminic acid residue-cleaving enzyme (KDNase Sm) is a new sialidase that has been induced and purified from Sphingobacterium multivorum. Catalysis by this new sialidase has been studied by enzyme kinetics and 1H NMR spectroscopy. Vmax/Km values determined for synthetic and natural substrates of KDNase Sm reveal that 4-methylumbelliferyl-KDN (KDNalpha2MeUmb, Vmax/Km = 0.033 min-1) is the best substrate for this sialidase, presumably because of its good leaving group properties. The transition state analogue, 2, 3-didehydro-2,3-dideoxy-D-galacto-D-glycero-nonulosonic acid, is a strong competitive inhibitor of KDNase Sm (Ki = 7.7 microM versus Km = 42 microM for KDNalpha2MeUmb). 2-Deoxy-2, 3-didehydro-N-acetylneuraminic acid and 2-deoxy-2, 3-didehydro-N-glycolylneuraminic acid are known to be strong competitive inhibitors for bacterial sialidases such as Arthrobacter ureafaciens sialidase; however, KDNase Sm activity is not significantly inhibited by these compounds. This observation suggests that the hydroxyl group at C-5 is important for recognition of the inhibitor by the enzyme. Reversible addition of water molecule (or hydroxide ion) to the reactive sialosyl cation, presumably formed at the catalytic site of KDNase Sm, eventually gives rise to two different adducts, the alpha- and beta-anomers of free 3-deoxy-D-glycero-D-galacto-nonulosonic acid. 1H NMR spectroscopic studies clearly demonstrate that the thermodynamically less stable alpha-form is preferentially formed as the first product of the cleavage reaction and that isomerization rapidly follows, leading to an equilibrium mixture of the two isomers, the beta-isomer being the major species at equilibrium. Therefore, we propose that KDNase Sm catalysis proceeds via a mechanism common to the known exosialidases, but the recognition of the substituent at C-5 by the enzyme differs.
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PMID:Catalysis by a new sialidase, deaminoneuraminic acid residue-cleaving enzyme (KDNase Sm), initially forms a less stable alpha-anomer of 3-deoxy-D-glycero-D-galacto-nonulosonic acid and is strongly inhibited by the transition state analogue, 2-deoxy-2, 3-didehydro-D-glycero-D-galacto-2-nonulopyranosonic acid, but not by 2-deoxy-2,3-didehydro-N-acetylneuraminic acid. 903 46

Various aryl and alkyl alpha-glycosides of KDN were synthesized and tested as substrates for their susceptibility to a deaminoneuraminic acid (KDN)-specific sialidase from Sphingobacterium multivorum, designated KDNase Sm. The synthetic KDN-glycosides were all hydrolyzed by the action of KDNase Sm. A hydroxyl group at C-5 position of KDN was required for the recognition by the enzyme, and was shown not to be replaced by an amino- or an acylamino group for the enzymatic recognition. These synthetic KDN-glycosides were also examined for their inducing activity of KDNase in S. multivorum and were shown to induce the KDNase activity effectively when the bacterium was cultured minimum salt medium containing both 0.1% glucose and 0.1% various KDN-glycosides. No KDNase activity was induced by the KDN-glycosides without 0.1% glucose. This is the first case of using synthetic KDN-glycosides as inducers of KDNase Sm.
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PMID:Induction of KDNase Sm, a deaminoneuraminic acid (KDN) residue-specific sialidase from Sphingobacterium multivorum, using synthetic KDN-glycosides. 970 55

KDN (2-keto-3-deoxy-D-glycero-D-galacto-nononic acid), a sialic acid analog, has been found to be widely distributed in nature. Despite the structural similarity between KDN and Neu5Ac, alpha-ketosides of KDN are refractory to conventional sialidases. We found that the hepatopancreas of the oyster, Crassostrea virginica, contains two KDN-cleaving sialidases but is devoid of conventional sialidase. The major sialidase, KDN-sialidase, effectively cleaves alpha-ketosidically linked KDN and also slowly cleaves the alpha-ketosides of Neu5Ac. The minor sialidase, KDNase, is specific for alpha-ketosides of KDN. We were able to separate these two KDN-cleaving enzymes using hydrophobic interaction and cation-exchange chromatographies. The rate of hydrolysis of 4-methylumbelliferyl-alpha-KDN (MU-KDN) by KDN-sialidase is 30 times faster than that of MU-Neu5Ac in the presence of 0.2 M NaCl, whereas in the absence of NaCl this ratio is only 8. KDNase hydrolyzes MU-KDN over 500 times faster than MU-Neu5Ac and is not affected by NaCl. KDN-sialidase purified to electrophoretically homogeneous form was found to have a molecular mass of 25 kDa and an isoelectric point of 8.4. One of the three tryptic peptides derived from KDN-sialidase contains the consensus motif, SXDXGXTW, that has been found in all conventional sialidases. Kinetic analysis of the inhibition of the hydrolysis of MU-KDN and MU-Neu5Ac by 2, 3-dehydro-2-deoxy-KDN (KDN2-en) and 2,3-dehydro-2-deoxy-(Neu5Ac2-en) suggests that KDN-sialidase contains two separate active sites for the hydrolysis of KDN and Neu5Ac. Both KDN-sialidase and KDNase effectively hydrolyze KDN-G(M3), KDNalpha2-->3Gal beta1-->4Glc, KDNalpha2-->6Galbeta1-->4Glc, KDNalpha2-->6-N-acetylgalactosaminitol, KDNalpha2-->6(KDNalpha2-->3)N-acetylgalactosaminitol, and KDNalpha2-->6(GlcNAcbeta1-->3)N-acetylgalactosaminitol. However, only KDN-sialidase also slowly hydrolyzes G(M3), Neu5Acalpha2-->3Galbeta1-->4Glc, and Neu5Acalpha2-->6Galbeta1-->4Glc. These two KDN-cleaving sialidases should be useful for studying the structure and function of KDN-containing glycoconjugates.
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PMID:2-Keto-3-deoxy-D-glycero-D-galacto-nononic acid (KDN)- and N-acetylneuraminic acid-cleaving sialidase (KDN-sialidase) and KDN-cleaving hydrolase (KDNase) from the hepatopancreas of oyster, Crassostrea virginica. 1054 27