Phosphodiesterase 3a

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Phosphodiesterase 3a

Existing structural data : 1lrc

Properties of human protein
Mass / length primary structure 1141 amino acids
Secondary to quaternary structure Peripheral membrane protein
Identifier
Gene name PDE3A
External IDs
Enzyme classification
EC, category 3.1.4.17 ,  phosphatase
Response type hydrolysis
Substrate cAMP, cGMP + H 2 O
Products 5'-AMP, 5'-GMP
Occurrence
Homology family PDE3
Parent taxon Euteleostomi

The phosphodiesterase -3a is an enzyme in vertebrates that the breakdown of cAMP causes. In humans it occurs in the heart muscle cells and in the female organism it allows the oocytes to  mature in prophase I. cGMP displaces cAMP from PDE3A and thus inhibits cAMP degradation.

Medical applications

By inhibiting phosphodiesterase, the contraction force of the heart can be increased (positive inotropic effect): the increased accumulation of cAMP in the heart muscle cell activates protein kinase A , which phosphorylates the calcium channel. As a result, it opens up more and more calcium can flow in, and the contraction force of the heart increases.

literature

  • E. Degerman, P. Belfrage, VC Manganiello: Structure, localization, and regulation of cGMP-inhibited phosphodiesterase (PDE3). In: J. Biol. Chem. 272 (11), March 1997, pp. 6823-6826. doi: 10.1074 / jbc.272.11.6823 . PMID 9102399 .
  • YH Jeon, YS Heo, CM Kim, YL Hyun, TG Lee, S. Ro, JM Cho: Phosphodiesterase: overview of protein structures, potential therapeutic applications and recent progress in drug development. In: Cell. Mol. Life Sci. 62 (11), June 2005, pp. 1198-1220. doi: 10.1007 / s00018-005-4533-5 . PMID 15798894 .
  • AT Bender, JA Beavo: Cyclic nucleotide phosphodiesterases: molecular regulation to clinical use. In: Pharmacol. Rev. 58 (3), September 2006, pp. 488-520. doi: 10.1124 / pr.58.3.5 . PMID 16968949 .
  • C. Lugnier: Cyclic nucleotide phosphodiesterase (PDE) superfamily: a new target for the development of specific therapeutic agents. In: Pharmacol. Ther. 109 (3), March 2006, pp. 366-398. doi: 10.1016 / j.pharmthera.2005.07.003 . PMID 16102838 .
  • DH Maurice, D. Palmer, DG Tilley et al: Cyclic nucleotide phosphodiesterase activity, expression, and targeting in cells of the cardiovascular system. In: Mol. Pharmacol. 64 (3), September 2003, pp. 533-546. doi: 10.1124 / mol.64.3.533 . PMID 12920188 .
  • M. Matthew: Isoform-Selective Inhibitors and Activators of PDE3 Cyclic Nucleotide Phosphodiesterases. WO 2003/012030: International patent application (PCT), World Intellectual Property Organization.
  • L. Massimiliana, G. Sandro, G. Alessandro: Pharmaceutical Compositions for the Treatment of Cellulite. WO 2006/063714: International patent application (PCT), World Intellectual Property Organization.
  • PW Erhardt, YL Chou: A topographical model for the c-AMP phosphodiesterase III active site. In: Life Sci. 49 (8), 1991, pp. 553-568. doi: 10.1016 / 0024-3205 (91) 90254-9 . PMID 1650876 .

Web links

Wikibooks: Biochemistry and Pathobiochemistry: Purine Metabolism  - Learning and Teaching Materials