2',3'-Cyclic-nucleotide 3'-phosphodiesterase

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2',3'-cyclic nucleotide 3' phosphodiesterase
Protein CNP PDB 1woj.png
PDB rendering based on 1woj.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols CNP ; CNP1
External IDs OMIM123830 MGI88437 HomoloGene7672 GeneCards: CNP Gene
EC number 3.1.4.37
RNA expression pattern
PBB GE CNP 208912 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1267 12799
Ensembl ENSG00000173786 ENSMUSG00000006782
UniProt P09543 P16330
RefSeq (mRNA) NM_033133 NM_001146318
RefSeq (protein) NP_149124 NP_001139790
Location (UCSC) Chr 17:
40.12 – 40.13 Mb
Chr 11:
100.57 – 100.59 Mb
PubMed search [1] [2]
2',3'-Cyclic-nucleotide 3'-phosphodiesterase
Identifiers
EC number 3.1.4.37
CAS number 60098-35-3
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / EGO

2',3'-Cyclic-nucleotide 3'-phosphodiesterase also known as CNPase is an enzyme that in humans is encoded by the CNP gene.[1][2]

Reaction[edit]

CNPase catalyzes the following reaction:

nucleoside 2',3'-cyclic phosphate + H2O \rightleftharpoons nucleoside 2'-phosphate

Thus, the two substrates of this enzyme are nucleoside 2',3'-cyclic phosphate and H2O, whereas its product is nucleoside 2'-phosphate.

Function[edit]

CNPase is a myelin-associated enzyme that makes up 4% of total CNS myelin protein, and is thought to undergo significant age-associated changes.[3] It is named for its ability to catalyze the phosphodiester hydrolysis of 2',3'-cyclic nucleotides to 2'-nucleotides, though a cohesive understanding of its specific physiologic functions are still ambiguous.[4]

Structural studies have revealed that four classes of CNPases belong to one protein superfamily. CNPase's catalytic core consists of three alpha-helices and nine beta-strands. The proposed mechanism of CNPases phosphodiesterase catalytic activity is similar to the second step of the reaction mechanism for RNase A.[5]

CNPase is expressed exclusively by oligodendrocytes in the CNS, and the appearance of CNPase seems to be one of the earliest events of oligodendrocyte differentiation.[6] CNPase is thought to play a critical role in the events leading up to myelination.[7]

CNPase also associates with microtubules in brain tissue and FRTL-5 thyroid cells, and is reported to have microtubule-associated protein-like activity (MAP; see MAP2), being able to catalyze microtubule formation at low molar ratios. Deletion of the C-terminus of CNPase or phosphorylation abolish the catalytic activity of microtubule formation. CNPase can link tubulin to cellular membranes, and might be involved in the regulation cytoplasmic microtubule distribution.[8]

Interestingly, CNPase has also been demonstrated to inhibit the replication of HIV-1 and other primate lentiviruses by binding the retroviral Gag protein and inhibiting the genesis of nascent viral particles. Whether this is a biological function of CNPase or a coincidental activity remains unclear [9]

References[edit]

  1. ^ Sprinkle TJ, Lanclos KD, Lapp DF (Aug 1992). "Assignment of the human 2',3'-cyclic nucleotide 3'-phosphohydrolase gene to chromosome 17". Genomics 13 (3): 877–80. doi:10.1016/0888-7543(92)90174-Q. PMID 1322358. 
  2. ^ "Entrez Gene: CNP 2',3'-cyclic nucleotide 3' phosphodiesterase". 
  3. ^ Hinman JD, Chen CD, Oh SY, Hollander W, Abraham CR (January 2008). "Age-dependent accumulation of ubiquitinated 2',3'-cyclic nucleotide 3'-phosphodiesterase in myelin lipid rafts". Glia 56 (1): 118–33. doi:10.1002/glia.20595. PMID 17963267. 
  4. ^ Kursula P (February 2008). "Structural properties of proteins specific to the myelin sheath". Amino Acids 34 (2): 175–85. doi:10.1007/s00726-006-0479-7. PMID 17177074. 
  5. ^ Sakamoto Y, Tanaka N, Ichimiya T, Kurihara T, Nakamura KT (February 2005). "Crystal structure of the catalytic fragment of human brain 2',3'-cyclic-nucleotide 3'-phosphodiesterase". J. Mol. Biol. 346 (3): 789–800. doi:10.1016/j.jmb.2004.12.024. PMID 15713463. 
  6. ^ Kasama-Yoshida H, Tohyama Y, Kurihara T, Sakuma M, Kojima H, Tamai Y (October 1997). "A comparative study of 2',3'-cyclic-nucleotide 3'-phosphodiesterase in vertebrates: cDNA cloning and amino acid sequences for chicken and bullfrog enzymes". J. Neurochem. 69 (4): 1335–42. doi:10.1046/j.1471-4159.1997.69041335.x. PMID 9326261. 
  7. ^ Gravel M, Peterson J, Yong VW, Kottis V, Trapp B, Braun PE (June 1996). "Overexpression of 2',3'-cyclic nucleotide 3'-phosphodiesterase in transgenic mice alters oligodendrocyte development and produces aberrant myelination". Mol. Cell. Neurosci. 7 (6): 453–66. doi:10.1006/mcne.1996.0033. PMID 8875429. 
  8. ^ Bifulco M, Laezza C, Stingo S, Wolff J (February 2002). "2',3'-Cyclic nucleotide 3'-phosphodiesterase: a membrane-bound, microtubule-associated protein and membrane anchor for tubulin". Proc. Natl. Acad. Sci. U.S.A. 99 (4): 5. doi:10.1073/pnas.042678799. PMC 122275. PMID 11842207. 
  9. ^ Wilson SJ, Schoggins JW, Zang T, Kutluay SB, Jouvenet N, Alim MA, Bitzegeio J, Rice CM, Bieniasz PD (October 2012). "Inhibition of HIV-1 particle assembly by 2',3'-cyclic-nucleotide 3'-phosphodiesterase.". Cell Host Microbe 12 (4): 585–97. doi:10.1016/j.chom.2012.08.012. PMC 3498451. PMID 23084924. 

Further reading[edit]