Literature summary for 3.1.3.16 extracted from

Peti, W.; Page, R.
Strategies to make protein serine/threonine (PP1, calcineurin) and tyrosine phosphatases (PTP1B) druggable Achieving specificity by targeting substrate and regulatory protein interaction sites (2015), Bioorg. Med. Chem., 23, 2781-2785 .

Search for more literature for 3.1.3.16

Inhibitors

Inhibitors	Comment	Organism	Structure
cyclosporin A	-	Homo sapiens
guanabenz	a small molecule drug that specifically inhibits translation by blocking the activity of elongation factor 2alpha (eIF2alpha) phosphatases, specifically CreP:PP1 and GADD34:PP1	Homo sapiens
microcystin	-	Homo sapiens
additional information	toxins that bind and block the PP1 active site are lethal, thus, potential drugs that target PP1 must interact outside the PP1 active site. The REG1:PP1 holoenzyme (REG1 represents a PP1 regulatory protein that contains an RVxF-PhiPhi-Arg motif, such as PNUTS) is preferentially populated compared to the REG2:PP1 holoenzyme (REG2 is a PP1 regulatory protein with only an RVxF motif), because the affinity of REG1 for PP1 is much higher than REG2 for PP1. A drug that targets only the PhiPhi-Arg binding grooves will selectively displace the motifs in REG1 that bind at these sites, thereby reducing the affinity of REG1 for PP1 and, consequently, increase the likelihood of forming REG2:PP1 holoenzymes. In this way, dephosphorylation of REG1:PP1 substrates will decrease while REG2:PP1 holoenzymes will increase	Homo sapiens
nodularin	-	Homo sapiens
okadaic acid	-	Homo sapiens
salubrinal	a small molecule drug that specifically inhibits translation by blocking the activity of elongation factor 2alpha (eIF2alpha) phosphatases, specifically CreP:PP1 and GADD34:PP1	Homo sapiens
swine fever virus protein A238L	an African swine fever virus protein, inhibits the enzyme not by blocking its active site, but instead by binding to calcineurin substrate recognition grooves, which blocks calcineurin from binding and dephosphorylating its substrates. A238L binds calcineurin via both a PxIxIT sequence and an LxVP sequence, overview	Homo sapiens
tacrolimus	i.e. FK506; i.e. FK506	Homo sapiens
tautomycin	-	Homo sapiens

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Ca2+	required for enzyme activity	Homo sapiens

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
[elongation factor 2alpha]-serine/threonine phosphate + H2O	Homo sapiens	-	[elongation factor 2alpha]-serine/threonine + phosphate	-	?

Organism

Organism	UniProt	Comment	Textmining
Homo sapiens	P62136	catalytic subunit alpha	-
Homo sapiens	Q08209	catalytic subunit alpha	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
additional information	although the specificity of the PP1 catalytic domains is low, PP1 dephosphorylates its substrates with high specificity. To achieve this, PP1 interacts with more than 100 distinct regulatory subunits, namely, inhibitory proteins that potently inhibit phosphatase activity by binding and blocking the active site, and targeting proteins, proteins that localize PP1 to distinct regions of the cell while also directly modulating PP1-substrate interactions. Many PP1 targeting subunits, such as NIPP1, enhance the binding of specific substrates. PP1 substrates bind directly to enzyme PP1, bind to other domains that are part of the PP1 regulatory proteins to enhance dephosphorylation or are dephosphorylated because PP1 is localized in proximity to the substrate via its targeting proteins	Homo sapiens	?	-	?
additional information	calcineurin is regulated by calcium, which is required for activation. Calcineurin binds directly to its substrates via protein interaction motifs that are also used by regulatory proteins	Homo sapiens	?	-	?
[elongation factor 2alpha]-serine/threonine phosphate + H2O	-	Homo sapiens	[elongation factor 2alpha]-serine/threonine + phosphate	-	?

Synonyms

Synonyms	Comment	Organism
calcineurin	-	Homo sapiens
eIF2alpha phosphatase	-	Homo sapiens
PP1	-	Homo sapiens
protein phosphatase 1	-	Homo sapiens
protein serine/threonine	-	Homo sapiens

General Information

General Information	Comment	Organism
malfunction	toxins that bind and block the PP1 active site are lethal, thus, potential drugs that target PP1 must interact outside the PP1 active site	Homo sapiens

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Release 2023.1 (January 2023)