KEGG   ENZYME: 2.1.1.106
Entry
EC 2.1.1.106                Enzyme                                 
Name
tryptophan 2-C-methyltransferase;
tsrM (gene name);
tryptophan 2-methyltransferase;
S-adenosylmethionine:tryptophan 2-methyltransferase
Class
Transferases;
Transferring one-carbon groups;
Methyltransferases
Sysname
S-adenosyl-L-methionine:L-tryptophan 2-C-methyltransferase
Reaction(IUBMB)
S-adenosyl-L-methionine + L-tryptophan = S-adenosyl-L-homocysteine + 2-methyl-L-tryptophan (overall reaction) [RN:R08547];
(1a) methylcob(III)alamin + L-tryptophan = cob(I)alamin + 2-methyl-L-tryptophan [RN:R13409];
(1b) S-adenosyl-L-methionine + cob(I)alamin = S-adenosyl-L-homocysteine + methylcob(III)alamin [RN:R13182]
Reaction(KEGG)
Substrate
S-adenosyl-L-methionine [CPD:C00019];
L-tryptophan [CPD:C00078];
methylcob(III)alamin [CPD:C06453];
cob(I)alamin [CPD:C00853]
Product
S-adenosyl-L-homocysteine [CPD:C00021];
2-methyl-L-tryptophan [CPD:C16831];
cob(I)alamin [CPD:C00853];
methylcob(III)alamin [CPD:C06453]
Comment
The enzyme, characterized from the bacterium Streptomyces laurentii, is involved in thiostrepton biosynthesis. It is a radical SAM enzyme that contains a [4Fe-4S] center and a methylcob(III)alamin cofactor. It has an exceptional reaction mechanism as the S-adenosyl-L-methionine (SAM) is not bound to the [4Fe-4S] center and does not produce a 5'-deoxyadenosyl radical but instead is believed to be involved in binding of the L-tryptophan substrate. After transfer of the methyl group from methylcob(III)alaminIn a methyl transfer from SAM to the generated cob(I)alamin takes place, preparing the enzyme for the next catalytic cycle. The original methyl group configuration is preserved.
History
EC 2.1.1.106 created 1992, modified 2024
Orthology
K21551  tryptophan 2-C-methyltransferase
Genes
SLAUSLA_3858
KSKKSE_17820
KISHUT16_07635(tsrT)
STRHGXP74_27185(tsrT)
ABRYNYE86_32855(tsrT)
NOABKM31_33400
AACDLWP59_01750(tsrT)
ATHML1857_04475(tsrT) L1857_13420(tsrT)
ABARAMYBAR_000360(tsrT)
KBRQ4V65_03190(tsrT) Q4V65_13535(tsrT)
UMERM788_45030(tsrT)
ASEACPL_3589
ACTSACWT_3461
AOUACTOB_007066(tsrT)
 » show all
Reference
1  [PMID:2321967]
  Authors
Frenzel T, Zhou P, Floss HG.
  Title
Formation of 2-methyltryptophan in the biosynthesis of thiostrepton: isolation of S-adenosylmethionine:tryptophan 2-methyltransferase.
  Journal
Arch Biochem Biophys 278:35-40 (1990)
DOI:10.1016/0003-9861(90)90227-P
Reference
2  [PMID:23064318]
  Authors
Pierre S, Guillot A, Benjdia A, Sandstrom C, Langella P, Berteau O
  Title
Thiostrepton tryptophan methyltransferase expands the chemistry of radical SAM enzymes.
  Journal
Nat Chem Biol 8:957-9 (2012)
DOI:10.1038/nchembio.1091
  Sequence
Reference
3  [PMID:26841310]
  Authors
Blaszczyk AJ, Silakov A, Zhang B, Maiocco SJ, Lanz ND, Kelly WL, Elliott SJ, Krebs C, Booker SJ
  Title
Spectroscopic and Electrochemical Characterization of the Iron-Sulfur and Cobalamin Cofactors of TsrM, an Unusual Radical S-Adenosylmethionine Methylase.
  Journal
J Am Chem Soc 138:3416-26 (2016)
DOI:10.1021/jacs.5b12592
Reference
4  [PMID:28747433]
  Authors
Blaszczyk AJ, Wang B, Silakov A, Ho JV, Booker SJ
  Title
Efficient methylation of C2 in l-tryptophan by the cobalamin-dependent radical S-adenosylmethionine methylase TsrM requires an unmodified N1 amine.
  Journal
J Biol Chem 292:15456-15467 (2017)
DOI:10.1074/jbc.M117.778548
Reference
5  [PMID:33462497]
  Authors
Knox HL, Chen PY, Blaszczyk AJ, Mukherjee A, Grove TL, Schwalm EL, Wang B, Drennan CL, Booker SJ.
  Title
Structural basis for non-radical catalysis by TsrM, a radical SAM methylase.
  Journal
Nat Chem Biol 17:485-491 (2021)
DOI:10.1038/s41589-020-00717-y
  Sequence
[ksk:KSE_17820]
Other DBs
ExplorEnz - The Enzyme Database: 2.1.1.106
IUBMB Enzyme Nomenclature: 2.1.1.106
ExPASy - ENZYME nomenclature database: 2.1.1.106
BRENDA, the Enzyme Database: 2.1.1.106
CAS: 126626-83-3

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