Occurrence of poly(alpha2,8-deaminoneuraminic acid) in mammalian tissues: widespread and developmentally regulated but highly selective expression on glycoproteins.

Ziak, Martin; Qu, Bao-Xi; Zuo, Xun; Zuber, Christian; Kanamori, Akira; Kitajima, Ken; Inoue, Sadako; Inoue, Yasuo; Roth, Jürgen

doi:10.1073/pnas.93.7.2759

Cited by 45 publications

(31 citation statements)

References 49 publications

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“…In mammals, KDN was first identified in various tissues including human lung carcinoma cells but at a much lower abundances than Neu5Ac (4) and was subsequently found on human red blood cells and ovarian cancer cells (5). The development of linkage-specific KDN antibodies (6,7) has allowed the identification of ␣2,8-linked polyKDN in many mammalian tissues (8), including the human lung (9).…”

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confidence: 99%

The Aspergillus fumigatus Sialidase Is a 3-Deoxy-d-glycero-d-galacto-2-nonulosonic Acid Hydrolase (KDNase)

Telford

Yeung²,

et al. 2011

Journal of Biological Chemistry

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Aspergillus fumigatus is a filamentous fungus that can cause severe respiratory disease in immunocompromised individuals. A putative sialidase from A. fumigatus was recently cloned and shown to be relatively poor in cleaving N-acetylneuraminic acid (Neu5Ac) in comparison with bacterial sialidases. Here we present the first crystal structure of a fungal sialidase. When the apo structure was compared with bacterial sialidase structures, the active site of the Aspergillus enzyme suggested that Neu5Ac would be a poor substrate because of a smaller pocket that normally accommodates the acetamido group of Neu5Ac in sialidases. A sialic acid with a hydroxyl in place of an acetamido group is 2-keto-3-deoxynononic acid (KDN). We show that KDN is the preferred substrate for the A. fumigatus sialidase and that A. fumigatus can utilize KDN as a sole carbon source. A 1.45-Å resolution crystal structure of the enzyme in complex with KDN reveals KDN in the active site in a boat conformation and nearby a second binding site occupied by KDN in a chair conformation, suggesting that polyKDN may be a natural substrate. The enzyme is not inhibited by the sialidase transition state analog 2-deoxy-2,3-dehydro-N-acetylneuraminic acid (Neu5Ac2en) but is inhibited by the related 2,3-didehydro-2,3-dideoxy-D-glycero-D-galacto-nonulosonic acid that we show bound to the enzyme in a 1.84-Å resolution crystal structure. Using a fluorinated KDN substrate, we present a 1.5-Å resolution structure of a covalently bound catalytic intermediate. The A. fumigatus sialidase is therefore a KDNase with a similar catalytic mechanism to Neu5Ac exosialidases, and this study represents the first structure of a KDNase.

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confidence: 99%

The Aspergillus fumigatus Sialidase Is a 3-Deoxy-d-glycero-d-galacto-2-nonulosonic Acid Hydrolase (KDNase)

Telford

Yeung²,

et al. 2011

Journal of Biological Chemistry

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“…Following the first report of KDN in 1986 (1), its association with a diverse number of living organisms ranging from bacterial capsular polysaccharide (2) to animal glycoproteins and glycolipids (3)(4)(5)(6)(7)(8)(9)(10)(11) has been demonstrated. Interestingly, immunochemical techniques suggested the presence of an oligomeric form of ␣238-linked KDN in mammalian tissues (10,11), and the occurrence of KDN residues was confirmed by biochemical and chemical methods (12). A unique feature of KDN-containing glycoconjugates is their complete resistance to the action of the known bacterial and viral exosialidases (1,5,9,13).…”

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confidence: 99%

Catalysis by a New Sialidase, Deaminoneuraminic Acid Residue-cleaving Enzyme (KDNase Sm), Initially Forms a Less Stable α-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

Terada

Kitajima

Inoue

et al. 1997

Journal of Biological Chemistry

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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 1 H NMR spectroscopy. V max /K m values determined for synthetic and natural substrates of KDNase Sm reveal that 4-methylumbelliferyl-KDN (KDN␣2MeUmb, V max /K m ‫؍‬ 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 (K i ‫؍‬ 7.7 M versus K m ‫؍‬ 42 M for KDN␣2MeUmb). 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 ␣-and ␤-anomers of free 3-deoxy-D-glycero-D-galacto-nonulosonic acid. 1 H NMR spectroscopic studies clearly demonstrate that the thermodynamically less stable ␣-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 ␤-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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“…and a2!8-linked oligoKDN, respectively [50,51]. The two useful reagents, mAb.kdn8kdn and KDNase Sm, were used in our collaborating studies for immunohistochemical detection of a2!8-linked oligoKDN epitopes in different organs of rat [51,52]. The results obtained were the ®rst indication of the presence of KDN residues in mammalian tissues.…”

Section: Evidence For the Occurrence Of Kdn And Kdn Residues In Mammalsmentioning

confidence: 99%

“…Because, in our previous study [30,52], KDN was shown to be expressed in all of human lung cancer cell lines examined, we initiated a systematic survey of KDN in white blood cells, blood plasma, ascites uid, and ascites cells of patients of different types of cancer. The objectives of these studies are two-fold: one is to develop a possible utilization of levels of KDN as a reliable and useful method for monitoring Diversity in sialic and polysialic acid residues 795 q1999 IUPAC, Pure Appl.…”

Section: Evidence For the Occurrence Of Kdn And Kdn Residues In Mammalsmentioning

confidence: 99%

Diversity in sialic and polysialic acid residues and related enzymes

Inoue¹,

Inoue²

1999

Pure and Applied Chemistry

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The occurrence of extensive diversity in the family of sialic acids is now well recognized but biological signi®cance of this diversity has been clari®ed only partially. In 1986 we showed natural occurrence of deaminated form of neuraminic acid, 2-keto-3-deoxy-Dglycero-D-galacto-nononic acid (KDN) as a capping residue of polysialyl chain of rainbow trout egg polysialoglycoprotein. Subsequent studies of our own and by others showed ubiquitous occurrence of KDN from bacteria to human although expression of this residue in large amounts was limited to certain species of animal. KDN was different from other families' of sialic acids usually denoted as modi®ed N-acylneuraminic acids of which O-acetyl substitution is most frequently found. The de®nition of sialic acid has to be changed by the ®nding of KDN.Prior to the ®nding of poly N-acetylneuraminic acid group in mammals, in 1978 we discovered poly N-glycolylneuraminic acid in rainbow trout eggs. This was the ®rst report of the occurrence of polysialic acid structure in animal glycoproteins. We also found the occurrence of polyKDN chains. All these ®ndings made signi®cant contribution to show that diversity of sialic acid family and especially diversity in polysialic acid structure are much more extensive and more ubiquitous than generally believed before. We showed that diversity of polysialic acid is not only originated from the diversity in building block but also the type of interresidue linkage. The diversity of sialic acid and polysialic acid is re¯ected in diversities in molecules that recognize these structures. We studied some of these molecules that speci®cally recognize different types of sialic acids and polysialic acids, and biosynthetic mechanism of polysialic acids.

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Occurrence of poly(alpha2,8-deaminoneuraminic acid) in mammalian tissues: widespread and developmentally regulated but highly selective expression on glycoproteins.

Abstract: In tissues of higher organisms homopoly-

Cited by 45 publications

References 49 publications

The Aspergillus fumigatus Sialidase Is a 3-Deoxy-d-glycero-d-galacto-2-nonulosonic Acid Hydrolase (KDNase)

The Aspergillus fumigatus Sialidase Is a 3-Deoxy-d-glycero-d-galacto-2-nonulosonic Acid Hydrolase (KDNase)

Diversity in sialic and polysialic acid residues and related enzymes

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