A0A286LEZ6 · PSIK_PSICY
- Protein4-hydroxytryptamine kinase
- GenepsiK
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids361 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score3/5
Function
function
4-hydroxytryptamine kinase; part of the gene cluster that mediates the biosynthesis of psilocybin, a psychotropic tryptamine-derived natural product (PubMed:28763571, PubMed:30283667).
The first step in the pathway is the decarboxylation of L-tryptophan to tryptamine by the decarboxylase psiD. PsiD does not decarboxylate phenylalanine, tyrosine, or 5-hydroxy- L -tryptophan (5-HTP) (PubMed:30283667).
4-hydroxy-L-tryptophan is accepted as substrate by psiD as well. The cytochrome P450 monooxygenase psiH then converts tryptamine to 4-hydroxytryptamine. The kinase psiK catalyzes the 4-O-phosphorylation step by converting 4-hydroxytryptamine into norbaeocystin. The methyltransferase psiM then catalyzes iterative methyl transfer to the amino group of norbaeocystin to yield psilocybin via a monomethylated intermediate, baeocystin. 4-hydroxy-6-methyl-l-tryptophancan also be converted the decarboxylase PsiD, kinase PsiK, and methyltransferase PsiM into respectively 6-methyl-norbaeocystin, 6-methylbaeocystin, and 6-methylpsilocybin (By similarity).
PsiK kinase can also turn psilocin into psilocybin (PubMed:35583969).
This activity may represent a protective mechanism to rephosphorylate the unstable psilocin to the stable psilocybin in case of intracellular ester cleavage (PubMed:35583969).
Moreover, psiK is able to O-phosphorylate the quaternary amine 4-hydroxy-N,N,N-trimethyltryptamine (4-OH-TMT) to yield aeruginascin, another bioactive compound found in Psilocybe species (PubMed:35583969).
The first step in the pathway is the decarboxylation of L-tryptophan to tryptamine by the decarboxylase psiD. PsiD does not decarboxylate phenylalanine, tyrosine, or 5-hydroxy- L -tryptophan (5-HTP) (PubMed:30283667).
4-hydroxy-L-tryptophan is accepted as substrate by psiD as well. The cytochrome P450 monooxygenase psiH then converts tryptamine to 4-hydroxytryptamine. The kinase psiK catalyzes the 4-O-phosphorylation step by converting 4-hydroxytryptamine into norbaeocystin. The methyltransferase psiM then catalyzes iterative methyl transfer to the amino group of norbaeocystin to yield psilocybin via a monomethylated intermediate, baeocystin. 4-hydroxy-6-methyl-l-tryptophancan also be converted the decarboxylase PsiD, kinase PsiK, and methyltransferase PsiM into respectively 6-methyl-norbaeocystin, 6-methylbaeocystin, and 6-methylpsilocybin (By similarity).
PsiK kinase can also turn psilocin into psilocybin (PubMed:35583969).
This activity may represent a protective mechanism to rephosphorylate the unstable psilocin to the stable psilocybin in case of intracellular ester cleavage (PubMed:35583969).
Moreover, psiK is able to O-phosphorylate the quaternary amine 4-hydroxy-N,N,N-trimethyltryptamine (4-OH-TMT) to yield aeruginascin, another bioactive compound found in Psilocybe species (PubMed:35583969).
Catalytic activity
- 4-hydroxytryptamine + ATP = 4-hydoxytryptamine 4-phosphate + ADP + H+This reaction proceeds in the forward direction.
- 4-hydroxy-N,N,N-trimethyltryptamine + ATP = ADP + aeruginascin + H+This reaction proceeds in the forward direction.
Cofactor
Biotechnology
The pharmaceutical interesting psilocybin as a treatment option against depression and anxiety is being investigated in advanced clinical trials.
Pathway
Secondary metabolite biosynthesis.
Features
Showing features for binding site, active site.
GO annotations
Aspect | Term | |
---|---|---|
Molecular Function | 4-hydroxytryptamine kinase activity | |
Molecular Function | ATP binding | |
Biological Process | psilocybin biosynthetic process |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended name4-hydroxytryptamine kinase
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Basidiomycota > Agaricomycotina > Agaricomycetes > Agaricomycetidae > Agaricales > Agaricineae > Strophariaceae > Psilocybe
Accessions
- Primary accessionA0A286LEZ6
Phenotypes & Variants
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000445828 | 1-361 | 4-hydroxytryptamine kinase | |||
Sequence: MTFDLKTEEGLLSYLTKHLSLDVAPNGVKRLSGGFVNVTWRVGLNAPYHGHTSIILKHAQPHLSSDIDFKIGVERSAYEYQALKIVSANSSLLGSSDIRVSVPEGLHYDVVNNALIMQDVGTMKTLLDYVTAKPPISAEIASLVGSQIGAFIARLHNLGRENKDKDDFKFFSGNIVGRTTADQLYQTIIPNAAKYGIDDPILPIVVKELVEEVMNSEETLIMADLWSGNILLQFDENSTELTRIWLVDWELCKYGPPSLDMGYFLGDCFLVARFQDQLVGTSMRQAYLKSYARNVKEPINYAKATAGIGAHLVMWTDFMKWGNDEEREEFVKKGVEAFHEANEDNRNGEITSILVKEASRT |
Interaction
Subunit
Monomer.
Structure
Sequence
- Sequence statusComplete
- Length361
- Mass (Da)40,315
- Last updated2017-11-22 v1
- ChecksumF3AD5838DA19F35A