8pb4
From Proteopedia
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<table><tr><td colspan='2'>[[8pb4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Psilocybe_cubensis Psilocybe cubensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8PB4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8PB4 FirstGlance]. <br> | <table><tr><td colspan='2'>[[8pb4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Psilocybe_cubensis Psilocybe cubensis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8PB4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8PB4 FirstGlance]. <br> | ||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 0.91Å</td></tr> | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 0.91Å</td></tr> | ||
| - | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=XP6: | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=SAH:S-ADENOSYL-L-HOMOCYSTEINE'>SAH</scene>, <scene name='pdbligand=XP6:[3-(2-azanylethyl)-1~{H}-indol-4-yl]+dihydrogen+phosphate'>XP6</scene></td></tr> |
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8pb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8pb4 OCA], [https://pdbe.org/8pb4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8pb4 RCSB], [https://www.ebi.ac.uk/pdbsum/8pb4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8pb4 ProSAT]</span></td></tr> | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=8pb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8pb4 OCA], [https://pdbe.org/8pb4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8pb4 RCSB], [https://www.ebi.ac.uk/pdbsum/8pb4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8pb4 ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | == Function == | ||
[https://www.uniprot.org/uniprot/PSIM_PSICU PSIM_PSICU] N-methyltransferase; part of the gene cluster that mediates the biosynthesis of psilocybin, a psychotropic tryptamine-derived natural product (PubMed:28763571, PubMed:31150155). The first step in the pathway is the decarboxylation of L-tryptophan to tryptamine by the decarboxylase psiD (PubMed:28763571, PubMed:31150155). 4-hydroxy-L-tryptophan is accepted as substrate by psiD as well (PubMed:28763571). The cytochrome P450 monooxygenase psiH then converts tryptamine to 4-hydroxytryptamine (PubMed:28763571). The kinase psiK catalyzes the 4-O-phosphorylation step by converting 4-hydroxytryptamine into norbaeocystin (PubMed:28763571, PubMed:31150155). The methyltransferase psiM then catalyzes iterative methyl transfer to the amino group of norbaeocystin to yield psilocybin via a monomethylated intermediate, baeocystin (PubMed:28763571, PubMed:31150155). 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 (PubMed:31150155).<ref>PMID:28763571</ref> <ref>PMID:31150155</ref> | [https://www.uniprot.org/uniprot/PSIM_PSICU PSIM_PSICU] N-methyltransferase; part of the gene cluster that mediates the biosynthesis of psilocybin, a psychotropic tryptamine-derived natural product (PubMed:28763571, PubMed:31150155). The first step in the pathway is the decarboxylation of L-tryptophan to tryptamine by the decarboxylase psiD (PubMed:28763571, PubMed:31150155). 4-hydroxy-L-tryptophan is accepted as substrate by psiD as well (PubMed:28763571). The cytochrome P450 monooxygenase psiH then converts tryptamine to 4-hydroxytryptamine (PubMed:28763571). The kinase psiK catalyzes the 4-O-phosphorylation step by converting 4-hydroxytryptamine into norbaeocystin (PubMed:28763571, PubMed:31150155). The methyltransferase psiM then catalyzes iterative methyl transfer to the amino group of norbaeocystin to yield psilocybin via a monomethylated intermediate, baeocystin (PubMed:28763571, PubMed:31150155). 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 (PubMed:31150155).<ref>PMID:28763571</ref> <ref>PMID:31150155</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Psilocybin, the natural hallucinogen produced by Psilocybe ("magic") mushrooms, holds great promise for the treatment of depression and several other mental health conditions. The final step in the psilocybin biosynthetic pathway, dimethylation of the tryptophan-derived intermediate norbaeocystin, is catalysed by PsiM. Here we present atomic resolution (0.9 A) crystal structures of PsiM trapped at various stages of its reaction cycle, providing detailed insight into the SAM-dependent methylation mechanism. Structural and phylogenetic analyses suggest that PsiM derives from epitranscriptomic N(6)-methyladenosine writers of the METTL16 family, which is further supported by the observation that bound substrates physicochemically mimic RNA. Inherent limitations of the ancestral monomethyltransferase scaffold hamper the efficiency of psilocybin assembly and leave PsiM incapable of catalysing trimethylation to aeruginascin. The results of our study will support bioengineering efforts aiming to create novel variants of psilocybin with improved therapeutic properties. | ||
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| + | Methyl transfer in psilocybin biosynthesis.,Hudspeth J, Rogge K, Dorner S, Mull M, Hoffmeister D, Rupp B, Werten S Nat Commun. 2024 Mar 28;15(1):2709. doi: 10.1038/s41467-024-46997-z. PMID:38548735<ref>PMID:38548735</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 8pb4" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Current revision
PsiM in complex with SAH and norbaeocystin, orthorhombic crystal form
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