Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TT85JMW)

• DTT Name: Bacterial Penicillin binding protein 3 (Bact mrcA)
• Synonyms: mrcA; Peptidoglycan synthetase ftsI; Peptidoglycan glycosyltransferase 3; Penicillin-binding protein 3; PSPB20; PBP-3; PBP 3
• Gene Name: Bact mrcA
• DTT Type: Successful target; [1]
• BioChemical Class: Hexosyltransferase
• UniProt ID: FTSI_ECOLI
• TTD ID: T33193
• EC Number: EC 3.4.16.4
• Sequence:
  MKAAAKTQKPKRQEEHANFISWRFALLCGCILLALAFLLGRVAWLQVISPDMLVKEGDMR
  SLRVQQVSTSRGMITDRSGRPLAVSVPVKAIWADPKEVHDAGGISVGDRWKALANALNIP
  LDQLSARINANPKGRFIYLARQVNPDMADYIKKLKLPGIHLREESRRYYPSGEVTAHLIG
  FTNVDSQGIEGVEKSFDKWLTGQPGERIVRKDRYGRVIEDISSTDSQAAHNLALSIDERL
  QALVYRELNNAVAFNKAESGSAVLVDVNTGEVLAMANSPSYNPNNLSGTPKEAMRNRTIT
  DVFEPGSTVKPMVVMTALQRGVVRENSVLNTIPYRINGHEIKDVARYSELTLTGVLQKSS
  NVGVSKLALAMPSSALVDTYSRFGLGKATNLGLVGERSGLYPQKQRWSDIERATFSFGYG
  LMVTPLQLARVYATIGSYGIYRPLSITKVDPPVPGERVFPESIVRTVVHMMESVALPGGG
  GVKAAIKGYRIAIKTGTAKKVGPDGRYINKYIAYTAGVAPASQPRFALVVVINDPQAGKY
  YGGAVSAPVFGAIMGGVLRTMNIEPDALTTGDKNEFVINQGEGTGGRS
• Function: Cell wall formation. Essential for the formation of a septum of the murein sacculus. Synthesis of cross-linked peptidoglycan from the lipid intermediates.
• KEGG Pathway:
  Peptidoglycan biosynthesis (ecj00550)
  Metabolic pathways (ecj01100)
  beta-Lactam resistance (ecj01501)
• BioCyc Pathway:
  MetaCyc:EG10341-MON
  EcoCyc:EG10341-MON

Molecular Interaction Atlas (MIA) of This DTT

7 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Aztreonam	DMDNJHG	Bacterial infection	1A00-1C4Z	Approved	[1]
Cefmenoxime	DMPLY7B	Bacterial infection	1A00-1C4Z	Approved	[2]
Cefmetazole	DM42W1B	Bacterial infection	1A00-1C4Z	Approved	[3]
Cefotiam	DMF5HU6	Respiratory tract infection	CA45	Approved	[4]
Latamoxef	DMANL0D	Bacterial infection	1A00-1C4Z	Approved	[3]
Mezlocillin	DMY5JEP	Acute gonococcal cervicitis		Approved	[5]
Moxalactam Disodium	DMYKUNR	Bacterial infection	1A00-1C4Z	Approved	[6]

2 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Benzylpenicillin	DMS9503	Actinomycosis		Phase 3	[7]
LYS228	DM23Y6K	Urinary tract infection	GC08	Phase 2	[8]

3 Investigative Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Acylureido penicillin mezlocillin	DM4CYKE	Discovery agent	N.A.	Investigative	[9]
Cephalosporin C	DMYW3ZG	Discovery agent	N.A.	Investigative	[10]
PCNOTAXIME GROUP	DMGS6YH	Discovery agent	N.A.	Investigative	[11]

References

• [1] Penicillin-binding protein PBP2 of Escherichia coli localizes preferentially in the lateral wall and at mid-cell in comparison with the old cell pole. Mol Microbiol. 2003 Jan;47(2):539-47.
• [2] In vitro evaluation of E1040, a new cephalosporin with potent antipseudomonal activity. Antimicrob Agents Chemother. 1988 May;32(5):693-701.
• [3] Clinical relevance of antibiotic-induced endotoxin release in patients undergoing hepatic resection. World J Surg. 1999 Jan;23(1):75-9.
• [4] Genetic analyses of beta-lactamase negative ampicillin-resistant strains of Haemophilus influenzae isolated in Okinawa, Japan. Jpn J Infect Dis. 2006 Feb;59(1):36-41.
• [5] Bactericidal effect of piperacillin alone and combined. Presse Med. 1986 Dec 20;15(46):2297-302.
• [6] Moxalactam (6059-S), a new 1-oxa-beta-lactam: binding affinity for penicillin-binding proteins of Escherichia coli K-12.
• [7] Association of amino acid substitutions in penicillin-binding protein 3 with beta-lactam resistance in beta-lactamase-negative ampicillin-resistant Haemophilus influenzae. Antimicrob Agents Chemother. 2001 Jun;45(6):1693-9.
• [8] Mode of Action of the Monobactam LYS228 and Mechanisms Decreasing In Vitro Susceptibility in Escherichia coli and Klebsiella pneumoniae. Antimicrob Agents Chemother. 2018 Sep 24;62(10):e01200-18.
• [9] Microbiology, pharmacology, and clinical use of mezlocillin sodium. Pharmacotherapy. 1982 Nov-Dec;2(6):300-12.
• [10] DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.
• [11] The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.