Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTVZJ7G)

• DTT Name: Cystathionine beta-synthase (CBS)
• Synonyms: Serine sulfhydrase; Beta-thionase
• Gene Name: CBS
• DTT Type: Clinical trial target; [1]
• BioChemical Class: Alpha-carbonic anhydrase
• UniProt ID: CBS_HUMAN
• TTD ID: T85309
• EC Number: EC 4.2.1.22
• Sequence:
  MPSETPQAEVGPTGCPHRSGPHSAKGSLEKGSPEDKEAKEPLWIRPDAPSRCTWQLGRPA
  SESPHHHTAPAKSPKILPDILKKIGDTPMVRINKIGKKFGLKCELLAKCEFFNAGGSVKD
  RISLRMIEDAERDGTLKPGDTIIEPTSGNTGIGLALAAAVRGYRCIIVMPEKMSSEKVDV
  LRALGAEIVRTPTNARFDSPESHVGVAWRLKNEIPNSHILDQYRNASNPLAHYDTTADEI
  LQQCDGKLDMLVASVGTGGTITGIARKLKEKCPGCRIIGVDPEGSILAEPEELNQTEQTT
  YEVEGIGYDFIPTVLDRTVVDKWFKSNDEEAFTFARMLIAQEGLLCGGSAGSTVAVAVKA
  AQELQEGQRCVVILPDSVRNYMTKFLSDRWMLQKGFLKEEDLTEKKPWWWHLRVQELGLS
  APLTVLPTITCGHTIEILREKGFDQAPVVDEAGVILGMVTLGNMLSSLLAGKVQPSDQVG
  KVIYKQFKQIRLTDTLGRLSHILEMDHFALVVHEQIQYHSTGKSSQRQMVFGVVTAIDLL
  NFVAAQERDQK
• Function: Hydro-lyase catalyzing the first step of the transsulfuration pathway, where the hydroxyl group of L-serine is displaced by L-homocysteine in a beta-replacement reaction to form L-cystathionine, the precursor of L-cysteine. This catabolic route allows the elimination of L-methionine and the toxic metabolite L-homocysteine. Also involved in the production of hydrogen sulfide, a gasotransmitter with signaling and cytoprotective effects on neurons.
• KEGG Pathway:
  Glycine, serine and threonine metabolism (hsa00260)
  Cysteine and methionine metabolism (hsa00270)
  Metabolic pathways (hsa01100)
  Biosynthesis of antibiotics (hsa01130)
  Biosynthesis of amino acids (hsa01230)
• Reactome Pathway:
  Metabolism of ingested SeMet, Sec, MeSec into H2Se (R-HSA-2408508)
  Cysteine formation from homocysteine (R-HSA-1614603)
• BioCyc Pathway: MetaCyc:HS08461-MON

Molecular Interaction Atlas (MIA) of This DTT

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
OT-58	DMWCJ1F	Homocystinuria	5C50.B	Phase 1/2	[2]

2 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
aminooxyacetic acid	DMHNDTW	Discovery agent	N.A.	Investigative	[1]
Heme	DMGC287	Discovery agent	N.A.	Investigative	[3]

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

• DTT DME Name: Serine sulfhydrase (CBS) DME Info
• Gene Name: CBS

1 Approved Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[4]

References

• [1] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Target id: 1443).
• [2] Classical homocystinuria: From cystathionine beta-synthase deficiency to novel enzyme therapies. Biochimie. 2020 Jun;173:48-56.
• [3] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
• [4] Association of genetic variation in cystathionine-beta-synthase and arsenic metabolism. Environ Res. 2010 Aug;110(6):580-7.