Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTE5J6X)

• DTT Name: Diphosphomevalonate decarboxylase (MVD)
• Synonyms: Mevalonate pyrophosphate decarboxylase; Mevalonate (diphospho)decarboxylase; Mevalonate (diphospho)Diphosphomevalonate decarboxylasedecarboxylase; MVD
• Gene Name: MVD
• DTT Type: Literature-reported target; [1]
• BioChemical Class: Carbon-carbon lyase
• UniProt ID: MVD1_HUMAN
• TTD ID: T96862
• EC Number: EC 4.1.1.33
• Sequence:
  MASEKPLAAVTCTAPVNIAVIKYWGKRDEELVLPINSSLSVTLHQDQLKTTTTAVISKDF
  TEDRIWLNGREEDVGQPRLQACLREIRCLARKRRNSRDGDPLPSSLSCKVHVASVNNFPT
  AAGLASSAAGYACLAYTLARVYGVESDLSEVARRGSGSACRSLYGGFVEWQMGEQADGKD
  SIARQVAPESHWPELRVLILVVSAEKKLTGSTVGMRASVETSPLLRFRAESVVPARMAEM
  ARCIRERDFPSFAQLTMKDSNQFHATCLDTFPPISYLNAISWRIIHLVHRFNAHHGDTKV
  AYTFDAGPNAVIFTLDDTVAEFVAAVWHGFPPGSNGDTFLKGLQVRPAPLSAELQAALAM
  EPTPGGVKYIIVTQVGPGPQILDDPCAHLLGPDGLPKPAA
• Function: Performs the first committed step in the biosynthesis of isoprenes.
• KEGG Pathway:
  Terpenoid backbone biosynthesis (hsa00900)
  Metabolic pathways (hsa01100)
• Reactome Pathway:
  Activation of gene expression by SREBF (SREBP) (R-HSA-2426168)
  Cholesterol biosynthesis (R-HSA-191273)
• BioCyc Pathway: MetaCyc:ENSG00000167508-MON

Molecular Interaction Atlas (MIA) of This DTT

12 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2,2-difluoromevalonate 5-diphosphate	DMKXFDA	Discovery agent	N.A.	Investigative	[2]
2-fluoromevalonate 5-diphosphate	DMEQRHY	Discovery agent	N.A.	Investigative	[3]
6-fluoromevalonate 5-diphosphate	DMPZ92X	Discovery agent	N.A.	Investigative	[1]
6-fluoromevalonate pyrophosphate	DMZ26LS	Discovery agent	N.A.	Investigative	[4]
analog 3 (Vlattas et al., 1996)	DMMKGT4	Discovery agent	N.A.	Investigative	[4]
diphosphoglycolyl proline	DM28NIU	Discovery agent	N.A.	Investigative	[1]
P'-geranyl 2-fluoromevalonate 5-diphosphate	DMNY187	Discovery agent	N.A.	Investigative	[1]
P'-geranyl 3,5,7-trihydroxy-3-methylheptanate 7-diphosphate	DMJ4SIA	Discovery agent	N.A.	Investigative	[5]
P'-geranyl 3,5,8-trihydroxy-3-methyloctanate 8-diphosphate	DMO9BUR	Discovery agent	N.A.	Investigative	[5]
P'-geranyl 3,5,9-trihydroxy-3-methylnonanate 9-diphosphate	DM2395E	Discovery agent	N.A.	Investigative	[5]
PMID17888661C18	DMLPC17	Discovery agent	N.A.	Investigative	[2]
PMID17888661C19	DMRWTHA	Discovery agent	N.A.	Investigative	[2]

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

• DTT DME Name: Mevalonate pyrophosphate decarboxylase (MPD) DME Info
• Gene Name: MVD

1 Investigative Drug(s) Metabolized by This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
(R)-5-diphosphomevalonate	DMOESL1	Discovery agent	N.A.	Investigative	[6]

References

• [1] Human mevalonate diphosphate decarboxylase: characterization, investigation of the mevalonate diphosphate binding site, and crystal structure. Arch Biochem Biophys. 2008 Dec 1;480(1):58-67.
• [2] Mutation and inhibition studies of mevalonate 5-diphosphate decarboxylase. Bioorg Med Chem Lett. 2007 Nov 15;17(22):6164-8.
• [3] Inhibition of mevalonate 5-diphosphate decarboxylase by fluorinated substrate analogs. Biochim Biophys Acta. 2006 Jul;1760(7):1080-7.
• [4] 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: 642).
• [5] Bifunctional inhibitors of mevalonate kinase and mevalonate 5-diphosphate decarboxylase. Org Lett. 2006 Mar 16;8(6):1013-6.
• [6] The Putative mevalonate diphosphate decarboxylase from Picrophilus torridus is in reality a mevalonate-3-kinase with high potential for bioproduction of isobutene. Appl Environ Microbiol. 2015 Apr;81(7):2625-34.