Phosphodiesterase 2

Structure of PDE2 with phosphate shown as sticks and catalytic metals as spheres. (PDB: 1Z1L​)

The PDE2 (phosphodiesterase 2) enzyme is one of 21 different phosphodiesterases (PDE) found in mammals. These different PDEs can be subdivided to 11 families (PDE1 – PDE11). The different PDEs of the same family are functionally related despite the fact that their amino acid sequences show considerable divergence.[1] The PDEs have different substrate specificities. Some are cAMP selective hydrolases (PDE 4, -7 and -8), others are cGMP selective hydrolases (PDE 5, -6 and -9) and the rest can hydrolyse both cAMP and cGMP (PDE1, -2, -3, -10 and -11).[2]

There is only one gene family coding for the PDE2, which is the PDE2A. Three splice variants have been found, the PDE2A1, PDE2A2 and PDE2A3 (PDE2A2 has only been found in rats). PDE2A1 is cytosolic whereas -A2 and -A3 are membrane bound. It has been suggested that different localization of PDE2A2 and -A3 is due to a unique N-terminal sequence, which is absent in PDE2A1. Despite the PDE2A splice variants being different, there is no known differences in their kinetic behavior.[3]

  1. ^ Iffland A, Kohls D, Low S, et al. (June 2005). "Structural determinants for inhibitor specificity and selectivity in PDE2A using the wheat germ in vitro translation system". Biochemistry. 44 (23): 8312–25. doi:10.1021/bi047313h. PMID 15938621.
  2. ^ Martinez SE, Wu AY, Glavas NA, et al. (October 2002). "The two GAF domains in phosphodiesterase 2A have distinct roles in dimerization and in cGMP binding". Proc. Natl. Acad. Sci. U.S.A. 99 (20): 13260–5. doi:10.1073/pnas.192374899. PMC 130621. PMID 12271124.
  3. ^ Bender AT, Beavo JA (September 2006). "Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use". Pharmacol. Rev. 58 (3): 488–520. doi:10.1124/pr.58.3.5. PMID 16968949. S2CID 7397281.