Neuraminidase

From Wikipedia, the free encyclopedia


Sialidase 1 (lysosomal sialidase)
Identifiers
Symbol(s) NEU1; NEU; SIAL1
External IDs OMIM: 608272 MGI: 97305 HomoloGene: 375
EC number 3.2.1.18
RNA expression pattern

More reference expression data
Orthologs
Human Mouse
Entrez 4758 18010
Ensembl ENSG00000184494 ENSMUSG00000007038
Uniprot Q99519 Q3UL64
Refseq NM_000434 (mRNA)
NP_000425 (protein)		 NM_010893 (mRNA)
NP_035023 (protein)
Location Chr c6_QBL: 31.96 - 31.96 Mb Chr 17: 34.54 - 34.54 Mb
Pubmed search [1] [2]

Sialidase 1 (lysosomal sialidase), also known as NEU1 or neuraminidase, is a human gene.[1]

The protein encoded by this gene encodes the lysosomal enzyme, which cleaves terminal sialic acid residues from substrates such as glycoproteins and glycolipids. In the lysosome, this enzyme is part of a heterotrimeric complex together with beta-galactosidase and cathepsin A (the latter also referred to as 'protective protein'). Mutations in this gene can lead to sialidosis.[1]

Neuraminidase is a glycoside hydrolase enzyme (EC 3.2.1.18). It is frequently found as an antigenic glycoprotein and is best known as one of the enzymes found on the surface of the Influenza virus. Some variants of the influenza neuraminidase confer more virulence to the virus than others. At least four sialidases (see NEU2, NEU3, NEU4) in the human genome have been described. Deficiencies in the human enzyme NEU1 leads to sialidosis, a rare lysosomal storage disease.

Contents

[edit] Subtypes

Swiss-Prot lists 137 types of neuraminidase from various species as of October 18, 2006.[2] Nine subtypes of influenza neuraminidase are known; many occur only in various species of duck and chicken. Subtypes N1 and N2 have been positively linked to epidemics in man, and strains with N3 or N7 subtypes have been identified in a number of isolated deaths[citation needed].

[edit] Structure

Influenza neuraminidase exists as a mushroom-shape projection on the surface of the influenza virus. It has a head consisting of four co-planar and roughly spherical subunits, and a hydrophobic region that is embedded within the interior of the virus' membrane. It comprises a single polypeptide chain that is oriented in the opposite direction to the hemagglutinin antigen. The composition of the polypeptide is a single chain of six conserved polar amino acids, followed by hydrophilic, variable amino acids.

[edit] Function

Neuraminidase has functions that aid in the efficiency of virus release from cells. Neuraminidase cleaves terminal neuraminic acid (also called sialic acid) residues from carbohydrate moieties on the surfaces of infected cells. This promotes the release of progeny viruses from infected cells. Neuraminidase also cleaves sialic acid residues from viral proteins, preventing aggregation of viruses. Administration of chemical inhibitors of neuraminidase is a treatment that limits the severity and spread of viral infections.

Neuraminidase is also a virulence factor for many bacteria including Bacteroides fragilis and Pseudomonas aeruginosa, where it is produced to cleave a sialic acid residue off ganglioside-GM1 (a modulator of cell surface and receptor activity) turning it into asialo-GM1 to which its type 4 pilli (attachment factors) bind preferentially.

Ideally influenza virus neuraminidase (NA) should act on the same type of virus receptor the virus Hemagglutinin (HA) binds to. This is not always so. It is not quite clear how the virus manages to function when there is no close match between the specificities of NA and HA.

Neuraminidase also plays a role in the beginning of influenza pathogenesis by cleaving sialic acid from the host glycoprotein and allowing the virus to enter the host (T-phages, macrophages, etc.).

In general, neuraminic acid residues are terminal and are therefore exo enzymes although an endoneuramidase is known as well.[3]

[edit] Neuraminidase inhibitors

Neuraminidase inhibitors are useful for combating influenza infection: zanamivir, administered by inhalation; oseltamivir, administered orally; and under research is peramivir administered parenterally, that is through intravenous or intramuscular injection.

[edit] See also

[edit] References

  1. ^ a b Entrez Gene: NEU1 sialidase 1 (lysosomal sialidase).
  2. ^ Search in UniProt Knowledgebase (Swiss-Prot and TrEMBL) for: neuraminidase
  3. ^ Definition: neuraminidase from Online Medical Dictionary

[edit] Further reading

  • Okamura-Oho Y, Zhang S, Callahan JW (1994). "The biochemistry and clinical features of galactosialidosis.". Biochim. Biophys. Acta 1225 (3): 244-54. PMID 8312369. 
  • Seyrantepe V, Poupetova H, Froissart R, et al. (2004). "Molecular pathology of NEU1 gene in sialidosis.". Hum. Mutat. 22 (5): 343-52. doi:10.1002/humu.10268. PMID 14517945. 
  • Verheijen FW, Palmeri S, Galjaard H (1987). "Purification and partial characterization of lysosomal neuraminidase from human placenta.". Eur. J. Biochem. 162 (1): 63-7. doi:10.1111/j.1432-1033.1987.tb10542.x. PMID 3102233. 
  • Verheijen FW, Palmeri S, Hoogeveen AT, Galjaard H (1985). "Human placental neuraminidase. Activation, stabilization and association with beta-galactosidase and its protective protein.". Eur. J. Biochem. 149 (2): 315-21. doi:10.1111/j.1432-1033.1985.tb08928.x. PMID 3922758. 
  • Hu H, Shioda T, Moriya C, et al. (1996). "Infectivities of human and other primate lentiviruses are activated by desialylation of the virion surface.". J. Virol. 70 (11): 7462-70. PMID 8892864. 
  • Pshezhetsky AV, Potier M (1996). "Association of N-acetylgalactosamine-6-sulfate sulfatase with the multienzyme lysosomal complex of beta-galactosidase, cathepsin A, and neuraminidase. Possible implication for intralysosomal catabolism of keratan sulfate.". J. Biol. Chem. 271 (45): 28359-65. doi:10.1074/jbc.271.45.28359. PMID 8910459. 
  • Bonten E, van der Spoel A, Fornerod M, et al. (1997). "Characterization of human lysosomal neuraminidase defines the molecular basis of the metabolic storage disorder sialidosis.". Genes Dev. 10 (24): 3156-69. doi:10.1101/gad.10.24.3156. PMID 8985184. 
  • Milner CM, Smith SV, Carrillo MB, et al. (1997). "Identification of a sialidase encoded in the human major histocompatibility complex.". J. Biol. Chem. 272 (7): 4549-58. doi:10.1074/jbc.272.7.4549. PMID 9020182. 
  • Pshezhetsky AV, Richard C, Michaud L, et al. (1997). "Cloning, expression and chromosomal mapping of human lysosomal sialidase and characterization of mutations in sialidosis.". Nat. Genet. 15 (3): 316-20. doi:10.1038/ng0397-316. PMID 9054950. 
  • Vinogradova MV, Michaud L, Mezentsev AV, et al. (1998). "Molecular mechanism of lysosomal sialidase deficiency in galactosialidosis involves its rapid degradation.". Biochem. J. 330 ( Pt 2): 641-50. PMID 9480870. 
  • van der Spoel A, Bonten E, d'Azzo A (1998). "Transport of human lysosomal neuraminidase to mature lysosomes requires protective protein/cathepsin A.". EMBO J. 17 (6): 1588-97. doi:10.1093/emboj/17.6.1588. PMID 9501080. 
  • Lukong KE, Elsliger MA, Chang Y, et al. (2000). "Characterization of the sialidase molecular defects in sialidosis patients suggests the structural organization of the lysosomal multienzyme complex.". Hum. Mol. Genet. 9 (7): 1075-85. doi:10.1093/hmg/9.7.1075. PMID 10767332. 
  • Naganawa Y, Itoh K, Shimmoto M, et al. (2000). "Molecular and structural studies of Japanese patients with sialidosis type 1.". J. Hum. Genet. 45 (4): 241-9. doi:10.1007/s100380070034. PMID 10944856. 
  • Bonten EJ, Arts WF, Beck M, et al. (2000). "Novel mutations in lysosomal neuraminidase identify functional domains and determine clinical severity in sialidosis.". Hum. Mol. Genet. 9 (18): 2715-25. doi:10.1093/hmg/9.18.2715. PMID 11063730. 
  • Lukong KE, Landry K, Elsliger MA, et al. (2001). "Mutations in sialidosis impair sialidase binding to the lysosomal multienzyme complex.". J. Biol. Chem. 276 (20): 17286-90. doi:10.1074/jbc.M100460200. PMID 11279074. 
  • Penzel R, Uhl J, Kopitz J, et al. (2001). "Splice donor site mutation in the lysosomal neuraminidase gene causing exon skipping and complete loss of enzyme activity in a sialidosis patient.". FEBS Lett. 501 (2-3): 135-8. doi:10.1016/S0014-5793(01)02645-X. PMID 11470272. 
  • Lukong KE, Seyrantepe V, Landry K, et al. (2002). "Intracellular distribution of lysosomal sialidase is controlled by the internalization signal in its cytoplasmic tail.". J. Biol. Chem. 276 (49): 46172-81. doi:10.1074/jbc.M104547200. PMID 11571282. 
  • Sergi C, Penzel R, Uhl J, et al. (2001). "Prenatal diagnosis and fetal pathology in a Turkish family harboring a novel nonsense mutation in the lysosomal alpha-N-acetyl-neuraminidase (sialidase) gene.". Hum. Genet. 109 (4): 421-8. doi:10.1007/s004390100592. PMID 11702224. 
  • Itoh K, Naganawa Y, Matsuzawa F, et al. (2002). "Novel missense mutations in the human lysosomal sialidase gene in sialidosis patients and prediction of structural alterations of mutant enzymes.". J. Hum. Genet. 47 (1): 29-37. doi:10.1007/s10038-002-8652-7. PMID 11829139. 

[edit] External links

v • d • e
Hydrolase: sugar hydrolases (EC 3.2)
3.2.1: Glycoside hydrolases
3.2.2: Hydrolysing N-Glycosyl compounds