cGMP-specific 3',5'-cyclic phosphodiesterase; cGMP-binding cGMP-specific phosphodiesterase; CGB-PDE (PDE5A)

Function

• plays a role in signal transduction by regulating the intracellular concentration of cyclic nucleotides
• catalyzes the specific hydrolysis of cGMP to 5'-GMP
• purine metabolism; 3',5'-cyclic GMP degradation; GMP from 3',5'-cyclic GMP: step 1/1
• phosphorylation is regulated by binding of cGMP to the two allosteric sites (putative)

guanosine 3',5'-cyclic phosphate + H2O = guanosine 5'-phosphate

Cofactor:

• binds 2 divalent metal cations per subunit
• site 1 may preferentially bind Zn+2
• site 2 has a preference for Mg+2 &/or Mn+2

Structure

• composed of a C-terminal catalytic domain containing two putative divalent metal sites & an N-terminal regulatory domain
• contains two homologous allosteric cGMP-binding regions, A & B
• belongs to the cyclic nucleotide phosphodiesterase family
• contains 2 GAF domains

Alternative splicing

named isoforms=2

Expression

• expressed in aortic smooth muscle cells, heart, placenta, skeletal muscle & pancreas
• lesser expression in brain, liver & lung

Pharmacology

• sildenafil (Viagra) used in treatment of erectile dysfunction is a highly selective & potent inhibitor of PDE5A
• also inhibited by zaprinast

More general terms

• phosphodiesterase 5; cGMP-specific phosphodiesterase

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=8654
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:8654
• OMIM: https://mirror.omim.org/entry/603310
• UniProt: http://www.uniprot.org/uniprot/O76074.html