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amino acid sequence for INMT

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benzyme

benzyme

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>gi|66933018|ref|NP_006765.4| indolethylamine N-methyltransferase [Homo sapiens]

MKGGFTGGDEYQKHFLPRDYLATYYSFDGSPSPEAEMLKFNLECLHKTFGPGGLQGDTLIDIGSGPTIYQ
VLAACDSFQDITLSDFTDRNREELEKWLKKEPGAYDWTPAVKFACELEGNSGRWEEKEEKLRAAVKRVLK
CDVHLGNPLAPAVLPLADCVLTLLAMECACCSLDAYRAALCNLASLLKPGGHLVTTVTLRLPSYMVGKRE
FSCVALEKEEVEQAVLDAGFDIEQLLHSPQSYSVTNAANNGVCFIVARKKPGP

and sequence for the mRNA transcript for INMT

>gi|66933017|ref|NM_006774.4| Homo sapiens indolethylamine N-methyltransferase (INMT), mRNA

ACATTTCAGGGACACCATGAAGGGTGGCTTCACTGGGGGTGATGAGTACCAGAAGCACTTCCTGCCCAGG
GACTACTTGGCTACTTACTACAGCTTCGATGGCAGCCCCTCACCCGAGGCCGAGATGCTGAAGTTTAACT
TGGAATGTCTCCACAAGACCTTCGGCCCTGGAGGCCTCCAAGGGGACACGCTGATTGACATTGGCTCAGG
TCCTACCATCTACCAAGTTCTTGCTGCCTGTGATTCCTTCCAAGACATCACTCTCTCCGACTTTACCGAC
CGCAACCGGGAGGAGCTGGAAAAGTGGCTGAAGAAGGAGCCGGGGGCCTATGACTGGACCCCAGCGGTGA
AATTCGCCTGTGAGCTGGAAGGAAACAGCGGCCGATGGGAGGAGAAGGAGGAGAAGCTGCGGGCAGCGGT
GAAGCGGGTGCTCAAGTGCGATGTCCACCTGGGCAACCCGCTGGCCCCGGCTGTGTTGCCTCTCGCCGAC
TGTGTGCTCACCCTGCTGGCCATGGAGTGTGCCTGCTGTAGCCTTGATGCCTACCGCGCTGCCCTGTGCA
ACCTTGCCTCACTGCTCAAGCCGGGTGGCCACCTGGTGACCACTGTCACGCTTCGGCTCCCGTCCTACAT
GGTGGGGAAGCGTGAATTTTCCTGCGTGGCCCTGGAGAAAGAGGAGGTGGAGCAGGCTGTCCTGGATGCT
GGCTTTGACATTGAACAGCTCCTACACAGTCCCCAGAGCTACTCTGTCACCAATGCTGCCAACAATGGGG
TCTGCTTCATTGTGGCTCGCAAGAAGCCTGGGCCCTGAGCCAGGAGGGCCAGCCAGAGGTCTGGTCAGGC
TGTGAGGCCTTGGCCATCTGTATGCTAGAGAGGGGTGAGGAATGGATACTGTCTAACAGTCTCTGATTTC
AACACTAACATTCCATCTTCTGAAATTCTGAGATTCTAACATCCTTGTTTTAGAATTCTAAGTTTCCAAC
ATTCCTCATTCTAGGATCCTAGGAGTGGAATTTTCCATTTTCTAATATACTAAGCCTTACAGCTATCTTA
GATGCGATCTGACTCCTGTGTGACTGTGGAGCACCCAGGGACGTGGTTTTAGAGTCTACCTAATATGTTA
AGGACAAGGAAACCTCTGAGTCTACCTAATATGTTAAGGACAAGGAAACCTCTGGACAGTGGTATATTGG
GGAATTTTTTTTTTTTTTTTGAGACGGAGTCTGGCTCTGTCACCCAGGCTAGAGTGCAATGGCACGATCT
CGGCTCACTGCAAGCTCTGCGTCCTGGGTTGACGCCATTCTCCTGCCTCAGCCTCCCGAGTAGCTGGGAC
TACAGGAGCTCGCCACCACACCCAGCTAATTTTTTTTTTTTTTTTTTTATTTGAGACGGAGTTTCGCTCT
GTCGCCCAGGCTGGAGTGCAGTGGCGCGATCTCGACTCACTGCAAGCTCCGCCTCCCGGGTTCACGCCAT
TCTCCTGCCTCAGCCTCCCGTGTAGCTGGGACTACAGGCACGCGCCACCATGCCCGGCTAATTTTTGTAT
TTTTAGTAGAGATGGGGTTTCACCGTGTTAGCCAGGATGGTCTCGATCTCCTGACCTGGTGATCCACCCA
CCTTGGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCGCACCCAGCCAGGGGGAATGTTCTATAA
CCAGCTCTGTAAAGGAAAAGCACTGATGTGTGGTAGTCACCAATTTCTGTGGTGTAAATACTCCCACCAT
GGTTGATTTCAAGCCACCAGTGGTTTAATAACCAGCTCATAAATCTCCTAAATATTTTACAGTTGACTCT
CATGAGCTGATTGGAGTCAGCTGGAACATACCACTGCCTCTAGACTAAGGTCAGCAGATTTAGCAAATAC
AGACTGCCCCAGTTCATTGAATTTTAGATAAATGAAATAAATCTATAAGGTTAAGTATGTCCCCAGAACT
GCATGGAACATGCTTAATCTAAACAATGATTTGTTGTTCACCTGAAATTCAAATTTAGCTGGGTGTCCTG
TATTTCATCTGGCAACCCTACTTCAGACCCAGGTGTAAGGTACATGGATGTGCTTTGGTCAAGGAATAGG
CCAAGGCAGAGATCCATGCCTGCATGACTCAGTGGGTTTGGTGCACAGGCACACACCTCCACTTGTTATA
TAACCTGTTTGTGTAAGTTCATACTTGGTCTGAGCCACTGTTGTCTGTAAAAGGTAATTGTCCTGCTAAT
GCTGTACAGGGGCTCTTGGGGTTCGGCTCAGCTCAACATGGCTTGACATGGTGGGCACACTGGCGCCCAG
TAAGAGAGAGAGAGAGCCAAAGCTGTCCGTTTTGCAGATGGACAGGAAGGAGCCAGGACACAGCTCAGCT
TGCTCACGCCCAGAGAGAGAAAAAGTTAAGCTGCTGACCCTGAAGGCAAGGGAGAGCAGGCTGCACAGCT
GTGTGTGGAAGCCACGGGCTCAAGCAGCCAAGGCAGGGCGGACAGTGTGAGAGAGCTAGTGTAAGCTGTT
GATGAGAGCTGTTGCTGAATAAAACCATATTCACCTGCCAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA
AAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA

INMT

2a14_bio_r_500.jpg
 
that's pretty awesome looking data. wish I could make sense from it.

what does this mean in your line of work? is this new research/data?
 
Benzy, more importantly, can you tell what's going on simply by looking at a huge chunk of text like that? :)

And can you please decant... I mean... elaborate further?
 
Noncompetitive Inhibition of Indolethylamine-N-methyltransferase by N,N-Dimethyltryptamine and N,N-Dimethylaminopropyltryptamine.

Abstract:
Indolethylamine-N-methyltransferase (INMT) is a Class 1 transmethylation enzyme known for its production of N,N-dimethyltryptamine (DMT), a hallucinogen with affinity for various serotonergic, adrenergic, histaminergic, dopaminergic, and sigma-1 receptors.

DMT is produced via the action of INMT on the endogenous substrates tryptamine and S-adenosyl-l-methionine (SAM). The biological, biochemical, and selective small molecule regulation of INMT enzyme activity remain largely unknown.

Kinetic mechanisms for inhibition of rabbit lung INMT (rabINMT) by the product, DMT, and by a new novel tryptamine derivative were determined. After Michaelis-Menten and Lineweaver-Burk analyses had been applied to study inhibition, DMT was found to be a mixed competitive and noncompetitive inhibitor when measured against tryptamine.

The novel tryptamine derivative, N-[2-(1H-indol-3-yl)ethyl]-N',N'-dimethylpropane-1,3-diamine (propyl dimethyl amino tryptamine or PDAT), was shown to inhibit rabINMT by a pure noncompetitive mechanism when measured against tryptamine with a Ki of 84 μM. No inhibition by PDAT was observed at 2 mM when it was tested against structurally similar Class 1 methyltransferases, such as human phenylethanolamine-N-methyltransferase (hPNMT) and human nicotinamide-N-methyltransferase (hNNMT), indicating selectivity for INMT.

The demonstration of noncompetitive mechanisms for INMT inhibition implies the presence of an inhibitory allosteric site. In silico analyses using the computer modeling software Autodock and the rabINMT sequence threaded onto the human INMT (hINMT) structure (Protein Data Bank entry 2A14 ) identified an N-terminal helix-loop-helix non-active site binding region of the enzyme. The energies for binding of DMT and PDAT to this region of rabINMT, as determined by Autodock, were -6.34 and -7.58 kcal/mol, respectively. Assessment of the allosteric control of INMT may illuminate new biochemical pathway(s) underlying the biology of INMT

Department of Neuroscience, University of Wisconsin School of Medicine and Public Health , 1300 University Avenue, Madison, Wisconsin 53706, United States.
 
Here is the amino acid sequence for the human 5HT2A receptor, in case anyone needs it:

>sp|P28223|5HT2A_HUMAN 5-hydroxytryptamine receptor 2A OS=Homo sapiens GN=HTR2A PE=1 SV=2
MDILCEENTSLSSTTNSLMQLNDDTRLYSNDFNSGEANTSDAFNWTVDSENRTNLSCEGC
LSPSCLSLLHLQEKNWSALLTAVVIILTIAGNILVIMAVSLEKKLQNATNYFLMSLAIAD
MLLGFLVMPVSMLTILYGYRWPLPSKLCAVWIYLDVLFSTASIMHLCAISLDRYVAIQNP
IHHSRFNSRTKAFLKIIAVWTISVGISMPIPVFGLQDDSKVFKEGSCLLADDNFVLIGSF
VSFFIPLTIMVITYFLTIKSLQKEATLCVSDLGTRAKLASFSFLPQSSLSSEKLFQRSIH
REPGSYTGRRTMQSISNEQKACKVLGIVFFLFVVMWCPFFITNIMAVICKESCNEDVIGA
LLNVFVWIGYLSSAVNPLVYTLFNKTYRSAFSRYIQCQYKENKKPLQLILVNTIPALAYK
SSQLQMGQKKNSKQDAKTTDNDCSMVALGKQHSEEASKDNSDGVNEKVSCV

I even made a fancy picture with I-TASSER
 

Attachments

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Question: how hard is it to insert the genes for a specific metabolic pathway into an organism that doesn't naturally express them?

It appears to be just 3 metabolic steps from L-tryptophan to DMT, so that means that, in theory, at least, we just need to insert the codes for 3 different enzymes into the genetic sequence.

What if we could do that for some kind of fast-growing, easy-to-care-for fungus (think like wood-ear mushrooms, you can buy grow-kits at the Whole Foods)? If that were the case, it would be easy and cheap to manufacture large quantities of DMT in a sustainable matter.

If we could get the sequences for other pathways that produce substituted tryptamines, there could be a whole world opening up of custom fungi.

Blessings
~ND
 
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