Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTUTO39)

• DTT Name: Methionine synthase (MTR)
• Synonyms: Methionine synthase, vitamin-B12dependent; MTR; MS; Cobalamin-dependent methionine synthase; B12 dependent methionine synthetase; 5-methyltetrahydrofolate:homocysteine methyltransferase; 5-methyltetrahydrofolate-homocysteine methyltransferase; 5-methyltetrahydrofolate homocysteine methyltransferase
• Gene Name: MTR
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Methyltransferase
• UniProt ID: METH_HUMAN
• TTD ID: T21661
• EC Number: EC 2.1.1.13
• Sequence:
  MSPALQDLSQPEGLKKTLRDEINAILQKRIMVLDGGMGTMIQREKLNEEHFRGQEFKDHA
  RPLKGNNDILSITQPDVIYQIHKEYLLAGADIIETNTFSSTSIAQADYGLEHLAYRMNMC
  SAGVARKAAEEVTLQTGIKRFVAGALGPTNKTLSVSPSVERPDYRNITFDELVEAYQEQA
  KGLLDGGVDILLIETIFDTANAKAALFALQNLFEEKYAPRPIFISGTIVDKSGRTLSGQT
  GEGFVISVSHGEPLCIGLNCALGAAEMRPFIEIIGKCTTAYVLCYPNAGLPNTFGDYDET
  PSMMAKHLKDFAMDGLVNIVGGCCGSTPDHIREIAEAVKNCKPRVPPATAFEGHMLLSGL
  EPFRIGPYTNFVNIGERCNVAGSRKFAKLIMAGNYEEALCVAKVQVEMGAQVLDVNMDDG
  MLDGPSAMTRFCNLIASEPDIAKVPLCIDSSNFAVIEAGLKCCQGKCIVNSISLKEGEDD
  FLEKARKIKKYGAAMVVMAFDEEGQATETDTKIRVCTRAYHLLVKKLGFNPNDIIFDPNI
  LTIGTGMEEHNLYAINFIHATKVIKETLPGARISGGLSNLSFSFRGMEAIREAMHGVFLY
  HAIKSGMDMGIVNAGNLPVYDDIHKELLQLCEDLIWNKDPEATEKLLRYAQTQGTGGKKV
  IQTDEWRNGPVEERLEYALVKGIEKHIIEDTEEARLNQKKYPRPLNIIEGPLMNGMKIVG
  DLFGAGKMFLPQVIKSARVMKKAVGHLIPFMEKEREETRVLNGTVEEEDPYQGTIVLATV
  KGDVHDIGKNIVGVVLGCNNFRVIDLGVMTPCDKILKAALDHKADIIGLSGLITPSLDEM
  IFVAKEMERLAIRIPLLIGGATTSKTHTAVKIAPRYSAPVIHVLDASKSVVVCSQLLDEN
  LKDEYFEEIMEEYEDIRQDHYESLKERRYLPLSQARKSGFQMDWLSEPHPVKPTFIGTQV
  FEDYDLQKLVDYIDWKPFFDVWQLRGKYPNRGFPKIFNDKTVGGEARKVYDDAHNMLNTL
  ISQKKLRARGVVGFWPAQSIQDDIHLYAEAAVPQAAEPIATFYGLRQQAEKDSASTEPYY
  CLSDFIAPLHSGIRDYLGLFAVACFGVEELSKAYEDDGDDYSSIMVKALGDRLAEAFAEE
  LHERVRRELWAYCGSEQLDVADLRRLRYKGIRPAPGYPSQPDHTEKLTMWRLADIEQSTG
  IRLTESLAMAPASAVSGLYFSNLKSKYFAVGKISKDQVEDYALRKNISVAEVEKWLGPIL
  GYDTD
• Function: Catalyzes the transfer of a methyl group from methyl- cobalamin to homocysteine, yielding enzyme-bound cob(I)alamin and methionine. Subsequently, remethylates the cofactor using methyltetrahydrofolate.
• KEGG Pathway:
  Cysteine and methionine metabolism (hsa00270)
  Selenocompound metabolism (hsa00450)
  One carbon pool by folate (hsa00670)
  Metabolic pathways (hsa01100)
  Biosynthesis of amino acids (hsa01230)
• Reactome Pathway:
  Sulfur amino acid metabolism (R-HSA-1614635)
  Defective MTRR causes HMAE (R-HSA-3359467)
  Defective MTR causes HMAG (R-HSA-3359469)
  RHOH GTPase cycle (R-HSA-9013407)
  Cobalamin (Cbl) metabolism (R-HSA-9759218)
  Methylation (R-HSA-156581)
• BioCyc Pathway: MetaCyc:HS04076-MON

The Drug-Metabolizing Enzyme (DME) Role of This DTT

• DTT DME Name: Vitamin B12 methionine synthase (MTR) DME Info
• Gene Name: MTR

2 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Folic Acid	DMEMBJC	Colorectal carcinoma		Approved	[2]
Levomefolic acid	DMUV5JB	N. A.	N. A.	Approved	[3]

References

• [1] Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34.
• [2] Metabolic derangement of methionine and folate metabolism in mice deficient in methionine synthase reductase. Mol Genet Metab. 2007 May;91(1):85-97.
• [3] Folic acid and L-5-methyltetrahydrofolate: comparison of clinical pharmacokinetics and pharmacodynamics. Clin Pharmacokinet. 2010 Aug;49(8):535-48.