Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTLP6GN)

• DTT Name: Bacterial DD-carboxypeptidase (Bact vanYB)
• Synonyms: vanYB; DD-peptidase; DD-carboxypeptidase; D-alanyl-D-alanine carboxypeptidase-transpeptidase
• Gene Name: Bact vanYB
• DTT Type: Successful target; [1]
• Related Disease: Bacterial infection [ICD-11: 1A00-1C4Z]
• BioChemical Class: Peptidase
• UniProt ID: VANY_ENTFA
• TTD ID: T64410
• EC Number: EC 3.4.16.4
• Sequence:
  MEKSNYHSNVNHHKRHMKQSGEKRAFLWAFIISFTVCTLFLGWRLVSVLEATQLPPIPAT
  HTGSGTGVAENPEENTLATAKEQGDEQEWSLILVNRQNPIPAQYDVELEQLSNGERIDIR
  ISPYLQDLFDAARADGVYPIVASGYRTTEKQQEIMDEKVAEYKAKGYTSAQAKAEAETWV
  AVPGTSEHQLGLAVDINADGIHSTGNEVYRWLDENSYRFGFIRRYPPDKTEITGVSNEPW
  HYRYVGIEAATKIYHQGLCLEEYLNTEK
• Function: Vancomycin-inducible, penicillin-resistant, DD- carboxypeptidase that hydrolyzes depsipeptide- and D-alanyl-D- alanine-containing peptidoglycan precursors. Insensitive to beta- lactams.
• KEGG Pathway:
  Peptidoglycan biosynthesis (efa00550)
  Metabolic pathways (efa01100)
  Vancomycin resistance (efa01502)
  Two-component system (efa02020)

Molecular Interaction Atlas (MIA) of This DTT

4 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
B-Lactams	DMR8YD6	Bacterial infection	1A00-1C4Z	Approved	[2]
Cefalotin	DMVYSLE	Bacterial infection	1A00-1C4Z	Approved	[3]
Cefotaxime	DMMKHBJ	Bacterial infection	1A00-1C4Z	Approved	[1], [3]
Cephalosporin	DM79XDW	Bacterial infection	1A00-1C4Z	Approved	[4]

1 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
TD-1792	DMGKBZH	Skin infection	1F28-1G0Z	Phase 3	[5]

10 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
2-[(Dioxidophosphino)Oxy]Benzoate	DMVSI6R	Discovery agent	N.A.	Investigative	[6]
3-boronobenzoic acid	DMRCJW0	Discovery agent	N.A.	Investigative	[7]
5-boronothiophene-2-carboxylic acid	DMPITR9	Discovery agent	N.A.	Investigative	[7]
Benzo[c][1,2]oxaborol-1(3H)-ol	DMZR02J	Discovery agent	N.A.	Investigative	[7]
Cephalosporin C	DMYW3ZG	Discovery agent	N.A.	Investigative	[8]
D-alanine	DMVIDQL	Discovery agent	N.A.	Investigative	[6]
Formaldehyde	DM7Q6M0	Discovery agent	N.A.	Investigative	[6]
Glycyl-L-Alpha-Amino-Epsilon-Pimelyl-D-Alanine	DM8FTJN	Discovery agent	N.A.	Investigative	[6]
NITROCEFIN	DM7M5VY	Discovery agent	N.A.	Investigative	[9]
Phenyl Boronic acid	DMFZH49	Discovery agent	N.A.	Investigative	[7]

References

• [1] Extended-spectrum cephalosporinases: structure, detection and epidemiology. Future Microbiol. 2007 Jun;2:297-307.
• [2] Has nature already identified all useful antibacterial targets Curr Opin Microbiol. 2008 Oct;11(5):387-92.
• [3] Binding of cephalothin and cefotaxime to D-ala-D-ala-peptidase reveals a functional basis of a natural mutation in a low-affinity penicillin-binding protein and in extended-spectrum beta-lactamases. Biochemistry. 1995 Jul 25;34(29):9532-40.
• [4] A 1.2-A snapshot of the final step of bacterial cell wall biosynthesis. Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):1427-31.
• [5] How many modes of action should an antibiotic have Curr Opin Pharmacol. 2008 Oct;8(5):564-73.
• [6] How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
• [7] Synthesis and evaluation of 3-(dihydroxyboryl)benzoic acids as D,D-carboxypeptidase R39 inhibitors. J Med Chem. 2009 Oct 8;52(19):6097-106.
• [8] DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.
• [9] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.