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

Reaction

CNPase catalyzes the following reaction:

:nucleoside 2′,3′-cyclic phosphate + H2O \rightleftharpoons nucleoside 2′-phosphate

Function

CNPase is a myelin-associated enzyme that makes up 4% of total CNS myelin protein, and is thought to undergo significant age-associated changes. 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.

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.

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. CNPase is thought to play a critical role in the events leading up to myelination.

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.

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.

References

References

1. (Jul 1992). "Assignment of the human 2′,3′-cyclic nucleotide 3′-phosphohydrolase gene to chromosome 17". Genomics.
2. "Entrez Gene: CNP 2′,3′-cyclic nucleotide 3′-phosphodiesterase".
3. (Jan 2008). "Age-dependent accumulation of ubiquitinated 2',3'-cyclic nucleotide 3'-phosphodiesterase in myelin lipid rafts". Glia.
4. (Feb 2008). "Structural properties of proteins specific to the myelin sheath". Amino Acids.
5. (Feb 2005). "Crystal structure of the catalytic fragment of human brain 2',3'-cyclic-nucleotide 3'-phosphodiesterase". Journal of Molecular Biology.
6. (Oct 1997). "A comparative study of 2',3'-cyclic-nucleotide 3'-phosphodiesterase in vertebrates: cDNA cloning and amino acid sequences for chicken and bullfrog enzymes". Journal of Neurochemistry.
7. (Jun 1996). "Overexpression of 2',3'-cyclic nucleotide 3'-phosphodiesterase in transgenic mice alters oligodendrocyte development and produces aberrant myelination". Molecular and Cellular Neurosciences.
8. (Feb 2002). "2',3'-Cyclic nucleotide 3'-phosphodiesterase: a membrane-bound, microtubule-associated protein and membrane anchor for tubulin". Proceedings of the National Academy of Sciences of the United States of America.
9. (Oct 2012). "Inhibition of HIV-1 particle assembly by 2′,3′-cyclic-nucleotide 3′-phosphodiesterase". Cell Host & Microbe.