cAMP-specific 3',5'-cyclic phosphodiesterase 4B is an enzyme that in humans is encoded by the PDE4B gene.[5]
This gene is a member of the type IV, cyclic AMP (cAMP)-specific, cyclic nucleotide phosphodiesterase (PDE) family. Cyclic nucleotides are important second messengers that regulate and mediate a number of cellular responses to extracellular signals, such as hormones, light, and neurotransmitters. The cyclic nucleotide phosphodiesterases (PDEs) regulate the cellular concentrations of cyclic nucleotides and thereby play a role in signal transduction. This gene encodes a protein that specifically hydrolyzes cAMP. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.[5][6]
Altered activity of this protein has been associated with schizophrenia and bipolar disorder.[5] PDE4B is believed to be the PDE4 subtype involved in the antipsychotic effects of PDE4 inhibitors such as rolipram.[7] PDE4B is involved in dopamine-associated and stress-related behaviours.[8] It has also recently been found to modulate cognition, as reduction in PDE4B activity improves memory and long-term plasticity in mouse models, possibly supporting further therapeutic applications.[9]
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This section needs to be updated. Please help update this article to reflect recent events or newly available information. (July 2023)
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Crisaborole, a boron-containing drug was approved by the FDA in 2016 for the treatment of atopic dermatitis, and as of 2024 is being commercialized by Pfizer under the name of Eucrisa (chemical name: 4-[(1-hydroxy-1,3-dihydro-2,1-benzoxaborol-5-yl)oxy]benzonitrile) mainly acting on PDE4B. [10][11][12]
PDB gallery
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1f0j: CATALYTIC DOMAIN OF HUMAN PHOSPHODIESTERASE 4B2B
1ro6: Crystal structure of PDE4B2B complexed with Rolipram (R &S)
1ro9: CRYSTAL STRUCTURES OF THE CATALYTIC DOMAIN OF PHOSPHODIESTERASE 4B2B COMPLEXED WITH 8-Br-AMP
1ror: CRYSTAL STRUCTURES OF THE CATALYTIC DOMAIN OF PHOSPHODIESTERASE 4B2B COMPLEXED WITH AMP
1tb5: Catalytic Domain Of Human Phosphodiesterase 4B In Complex With AMP
1xlx: Catalytic Domain Of Human Phosphodiesterase 4B In Complex With Cilomilast
1xlz: Catalytic Domain Of Human Phosphodiesterase 4B In Complex With Filaminast
1xm4: Catalytic Domain Of Human Phosphodiesterase 4B In Complex With Piclamilast
1xm6: Catalytic Domain Of Human Phosphodiesterase 4B In Complex With (R)-Mesopram
1xmu: Catalytic Domain Of Human Phosphodiesterase 4B In Complex With Roflumilast
1xmy: Catalytic Domain Of Human Phosphodiesterase 4B In Complex With (R)-Rolipram
1xn0: Catalytic Domain Of Human Phosphodiesterase 4B In Complex With (R,S)-Rolipram
1xos: Catalytic Domain Of Human Phosphodiesterase 4B In Complex With Sildenafil
1xot: Catalytic Domain Of Human Phosphodiesterase 4B In Complex With Vardenafil
1y2h: Catalytic Domain Of Human Phosphodiesterase 4B In Complex With 1-(2-chloro-phenyl)-3,5-dimethyl-1H-pyrazole-4-carboxylic acid ethyl ester
1y2j: Catalytic Domain Of Human Phosphodiesterase 4B In Complex With 3,5-dimethyl-1-(3-nitro-phenyl)-1H-pyrazole-4-carboxylic acid ethyl ester
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3.1.1: Carboxylic ester hydrolases |
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3.1.2: Thioesterase |
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3.1.3: Phosphatase |
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3.1.4: Phosphodiesterase |
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3.1.6: Sulfatase |
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Nuclease (includes deoxyribonuclease and ribonuclease) |
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