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GAF Domain
The GAF domain is a type of protein domain that is found in a wide range of proteins from all species. The GAF domain is named after some of the proteins it is found in: cGMP-specific phosphodiesterases, adenylyl cyclases and FhlA. The first structure of a GAF domain solved by Ho and colleagues showed that this domain shared a similar fold with the PAS domain. In mammals, GAF domains are found in five members of the cyclic nucleotide phosphodiesterase superfamily: PDE2, PDE5, and PDE6 which bind cGMP to the GAF domain, PDE10 which binds cAMP, and PDE11 which binds both cGMP and cAMP. Examples Human proteins containing this domain include: * PDE2A, PDE5A, PDE6A, PDE6B, PDE6C, PDE10A, PDE11A Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A is an enzyme that in humans is encoded by the ''PDE11A'' gene. The 3',5'-cyclic nucleotides cAMP and cGMP function as second messengers in a wide variety of signal transduction pathways. 3',5 ... References {{reflist Protein doma ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Protein Domain
In molecular biology, a protein domain is a region of a protein's polypeptide chain that is self-stabilizing and that folds independently from the rest. Each domain forms a compact folded three-dimensional structure. Many proteins consist of several domains, and a domain may appear in a variety of different proteins. Molecular evolution uses domains as building blocks and these may be recombined in different arrangements to create proteins with different functions. In general, domains vary in length from between about 50 amino acids up to 250 amino acids in length. The shortest domains, such as zinc fingers, are stabilized by metal ions or disulfide bridges. Domains often form functional units, such as the calcium-binding EF hand domain of calmodulin. Because they are independently stable, domains can be "swapped" by genetic engineering between one protein and another to make chimeric proteins. Background The concept of the domain was first proposed in 1973 by Wetlaufer aft ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PAS Domain
A Per-Arnt-Sim (PAS) domain is a protein domain found in all kingdoms of life. Generally, the PAS domain acts as a molecular sensor, whereby small molecules and other proteins associate via binding of the PAS domain. Due to this sensing capability, the PAS domain has been shown as the key structural motif involved in protein-protein interactions of the circadian clock, and it is also a common motif found in signaling proteins, where it functions as a signaling sensor. Discovery PAS domains are found in a large number of organisms from bacteria to mammals. The PAS domain was named after the three proteins in which it was first discovered: * Per – period circadian protein * Arnt – aryl hydrocarbon receptor nuclear translocator protein * Sim – single-minded protein Since the initial discovery of the PAS domain, a large quantity of PAS domain binding sites have been discovered in bacteria and eukaryotes. A subset called PAS LOV proteins are responsive to oxygen, light a ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CGMP-specific Phosphodiesterase Type 5
Cyclic guanosine monophosphate-specific phosphodiesterase type 5 is an enzyme () from the phosphodiesterase class. It is found in various tissues, most prominently the corpus cavernosum and the retina. It has also been recently discovered to play a vital role in the cardiovascular system. The phosphodiesterase (PDE) isozymes, found in several tissues including the rod and cone photoreceptor cells of the retina, belong to a large family of cyclic nucleotide PDEs that catalyze cAMP and cGMP hydrolysis. The interest in PDEs as molecular targets of drug action has grown with the development of isozyme-selective PDE inhibitors that offer potent inhibition of selected isozymes without the side-effects attributed to nonselective inhibitors such as theophylline. Sildenafil, vardenafil, tadalafil, and avanafil are PDE5 inhibitors that are significantly more potent and selective than zaprinast and other early PDE5 inhibitors. Action of PDE5 PDE5 is an enzyme that accepts cGMP and b ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PDE6A
Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha is an enzyme that in humans is encoded by the ''PDE6A'' gene. PDE6A encodes the cyclic-GMP ( cGMP) specific phosphodiesterase 6A alpha subunit, expressed in cells of the retinal rod outer segment. The phosphodiesterase 6 holoenzyme is a heterotrimer composed of an alpha, beta, and two gamma subunits.cGMP is an important regulator of rod cell membrane current, and its dynamic concentration is established by phosphodiesterase 6A cGMP hydrolysis and gunylate cyclase cGMP synthesis. Mutations in PDE6A have been identified as one cause of autosomal recessive retinitis pigmentosa Retinitis pigmentosa (RP) is a genetic disorder of the eyes that causes loss of vision. Symptoms include trouble seeing at night and decreasing peripheral vision (side and upper or lower visual field). As peripheral vision worsens, people may .... References Further reading * * * * * * * * * * * External links GeneReviews/NCBI/NIH/UW ent ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PDE6B
Rod cGMP-specific 3',5'-cyclic phosphodiesterase subunit beta is the beta subunit of the protein complex PDE6 that is encoded by the ''PDE6B'' gene. PDE6 is crucial in transmission and amplification of visual signal. The existence of this beta subunit is essential for normal PDE6 functioning. Mutations in this subunit are responsible for retinal degeneration such as retinitis pigmentosa or congenital stationary night blindness. Structure PDE6 is a protein complex located on the photoreceptor's outer segment, and plays an important role in the phototransduction cascade. There are two types of photoreceptors: cones and rods. The rod and cone PDE6 complexes have different structures. PDE6β together with PDE6α and two identical inhibitory subunits, PDE6γ, form the rod PDE6 holoenzyme while the cone PDE6 complex only consists of two identical PDE6α' catalytic subunits. PDE6β, one of the catalytic units in rod PDE6, is composed of three domains: two N-terminal GAF domains and ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PDE6C
Cone cGMP-specific 3',5'-cyclic phosphodiesterase subunit alpha' is an enzyme that in humans is encoded by the ''PDE6C'' gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba .... References Further reading * * * * * * * * * {{refend External links GeneReviews/NIH/NCBI/UW entry on Achromatopsia OMIM entries on Achromatopsia ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PDE10A
cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A is an enzyme that in humans is encoded by the ''PDE10A'' gene. Various cellular responses are regulated by the second messengers cAMP and cGMP. Phosphodiesterases, such as PDE10A, eliminate cAMP- and cGMP-mediated intracellular signaling by hydrolyzing the cyclic nucleotide to the corresponding nucleoside 5-prime monophosphate. Inhibitors * Compound 96: IC50 = 700 pM, high selectivity against all other members of the PDE family * Papaverine * PF-2545920 Mardepodect (developmental code name PF-2545920) is a drug which was developed by Pfizer for the treatment of schizophrenia. It acts as a phosphodiesterase inhibitor selective for the PDE10A subtype. The PDE10A enzyme is expressed primarily in ... * TAK-063: IC50 = 300 pM * AMG 579 Research Preliminary evidence indicates a possible link between PDE10A expression and obesity in mice and humans. References Further reading * * * * * * * * * * EC ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PDE11A
Dual 3',5'-cyclic-AMP and -GMP phosphodiesterase 11A is an enzyme that in humans is encoded by the ''PDE11A'' gene. The 3',5'-cyclic nucleotides cAMP and cGMP function as second messengers in a wide variety of signal transduction pathways. 3',5'-cyclic nucleotide phosphodiesterases (PDEs) catalyze the hydrolysis of cAMP and cGMP to the corresponding 5'-monophosphates and provide a mechanism to downregulate cAMP and cGMP signaling. This gene encodes a member of the PDE protein superfamily. Mutations in this gene are a cause of Cushing's disease and adrenocortical hyperplasia. Multiple transcript variants encoding different isoforms A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene or gene family and are the result of genetic differences. While many perform the same or similar biological roles, some isof ... have been found for this gene. Inhibitors * BC11-38 References Further reading * * * * * * * ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
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