Target Information
Target General Information | Top | |||||
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Target ID |
T33193
(Former ID: TTDS00212)
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Target Name |
Bacterial Penicillin binding protein 3 (Bact mrcA)
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Synonyms |
mrcA; Peptidoglycan synthetase ftsI; Peptidoglycan glycosyltransferase 3; Penicillin-binding protein 3; PSPB20; PBP-3; PBP 3
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Gene Name |
Bact mrcA
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Target Type |
Successful target
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[1] | ||||
Disease | [+] 3 Target-related Diseases | + | ||||
1 | Bacterial infection [ICD-11: 1A00-1C4Z] | |||||
2 | Respiratory infection [ICD-11: CA07-CA4Z] | |||||
3 | Urinary tract infection [ICD-11: GC08] | |||||
Function |
Cell wall formation. Essential for the formation of a septum of the murein sacculus. Synthesis of cross-linked peptidoglycan from the lipid intermediates.
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BioChemical Class |
Hexosyltransferase
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UniProt ID | ||||||
EC Number |
EC 3.4.16.4
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Sequence |
MKAAAKTQKPKRQEEHANFISWRFALLCGCILLALAFLLGRVAWLQVISPDMLVKEGDMR
SLRVQQVSTSRGMITDRSGRPLAVSVPVKAIWADPKEVHDAGGISVGDRWKALANALNIP LDQLSARINANPKGRFIYLARQVNPDMADYIKKLKLPGIHLREESRRYYPSGEVTAHLIG FTNVDSQGIEGVEKSFDKWLTGQPGERIVRKDRYGRVIEDISSTDSQAAHNLALSIDERL QALVYRELNNAVAFNKAESGSAVLVDVNTGEVLAMANSPSYNPNNLSGTPKEAMRNRTIT DVFEPGSTVKPMVVMTALQRGVVRENSVLNTIPYRINGHEIKDVARYSELTLTGVLQKSS NVGVSKLALAMPSSALVDTYSRFGLGKATNLGLVGERSGLYPQKQRWSDIERATFSFGYG LMVTPLQLARVYATIGSYGIYRPLSITKVDPPVPGERVFPESIVRTVVHMMESVALPGGG GVKAAIKGYRIAIKTGTAKKVGPDGRYINKYIAYTAGVAPASQPRFALVVVINDPQAGKY YGGAVSAPVFGAIMGGVLRTMNIEPDALTTGDKNEFVINQGEGTGGRS Click to Show/Hide
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Drugs and Modes of Action | Top | |||||
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Approved Drug(s) | [+] 7 Approved Drugs | + | ||||
1 | Aztreonam | Drug Info | Approved | Bacterial infection | [2] | |
2 | Cefmenoxime | Drug Info | Approved | Bacterial infection | [2] | |
3 | Cefmetazole | Drug Info | Approved | Bacterial infection | [3] | |
4 | Cefotiam | Drug Info | Approved | Respiratory tract infection | [2], [4] | |
5 | Latamoxef | Drug Info | Approved | Bacterial infection | [5] | |
6 | Mezlocillin | Drug Info | Approved | Urinary tract infection | [4], [6] | |
7 | Moxalactam Disodium | Drug Info | Approved | Bacterial infection | [4] | |
Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
1 | LYS228 | Drug Info | Phase 2 | Urinary tract infection | [7] | |
Mode of Action | [+] 4 Modes of Action | + | ||||
Binder | [+] 9 Binder drugs | + | ||||
1 | Aztreonam | Drug Info | [1] | |||
2 | Cefmenoxime | Drug Info | [8] | |||
3 | Cefmetazole | Drug Info | [5] | |||
4 | Cefotiam | Drug Info | [9] | |||
5 | Latamoxef | Drug Info | [5] | |||
6 | Mezlocillin | Drug Info | [10] | |||
7 | Benzylpenicillin | Drug Info | [12] | |||
8 | LYS228 | Drug Info | [13] | |||
9 | Acylureido penicillin mezlocillin | Drug Info | [14] | |||
Modulator | [+] 1 Modulator drugs | + | ||||
1 | Moxalactam Disodium | Drug Info | [11] | |||
Antagonist | [+] 1 Antagonist drugs | + | ||||
1 | Cephalosporin C | Drug Info | [15] | |||
Inhibitor | [+] 1 Inhibitor drugs | + | ||||
1 | PCNOTAXIME GROUP | Drug Info | [16] |
Drug Binding Sites of Target | Top | |||||
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Ligand Name: AIC499 (bound) | Ligand Info | |||||
Structure Description | Crystal structure of PBP3 from E. coli in complex with AIC499 | PDB:7ONW | ||||
Method | X-ray diffraction | Resolution | 2.70 Å | Mutation | No | [17] |
PDB Sequence |
LRVQQVSTSR
71 GMITDRSGRP81 LAVSVPVKAI91 WADPKEVHDA101 GGISVGDRWK111 ALANALNIPL 121 DQLSARINAN131 PKGRFIYLAR141 QVNPDMADYI151 KKLKLPGIHL161 REESRRYYPS 171 GEVTAHLIGF181 TNVDSQGIEG191 VEKSFDKWLT201 GQAAHNLALS235 IDERLQALVY 245 RELNNAVAFN255 KAESGSAVLV265 DVNTGEVLAM275 ANSPSYNPNN285 LSGTPKEAMR 295 NRTITDVFEP305 GSTVKPMVVM315 TALQRGVVRE325 NSVLNTIPYR335 INGHEIKDVA 345 RYSELTLTGV355 LQKSSNVGVS365 KLALAMPSSA375 LVDTYSRFGL385 GKATNLGLVG 395 ERSGLYPQKQ405 RWSDIERATF415 SFGYGLMVTP425 LQLARVYATI435 GSYGIYRPLS 445 ITKVDPPVPG455 ERVFPESIVR465 TVVHMMESVA475 LPGGGGVKAA485 IKGYRIAIKT 495 GTAKKVGPDG505 RYINKYIAYT515 AGVAPASQPR525 FALVVVINDP535 QAGKYYGGAV 545 SAPVFGAIMG555 GVLRTMNIEP565 DALTT
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GLU304
2.273
GLY306
3.225
SER307
1.458
THR308
4.974
LYS310
3.793
VAL344
3.264
SER359
3.315
ASN361
3.281
PHE417
3.100
GLY418
3.590
TYR419
3.319
LYS494
4.397
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Click to View More Binding Site Information of This Target with Different Ligands |
Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Similarity Proteins
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There is no similarity protein (E value < 0.005) for this target
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Drug Property Profile of Target | Top | |
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(1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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(3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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(5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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"RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five |
Target-Related Models and Studies | Top | |||||
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Target Validation |
References | Top | |||||
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REF 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. | |||||
REF 2 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
REF 3 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 050637. | |||||
REF 4 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
REF 5 | Clinical relevance of antibiotic-induced endotoxin release in patients undergoing hepatic resection. World J Surg. 1999 Jan;23(1):75-9. | |||||
REF 6 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 050549. | |||||
REF 7 | ClinicalTrials.gov (NCT03377426) LYS228 PK, Clinical Response, Safety and Tolerability in Patients With Complicated Urinary Tract Infection (cUTI). U.S. National Institutes of Health. | |||||
REF 8 | In vitro evaluation of E1040, a new cephalosporin with potent antipseudomonal activity. Antimicrob Agents Chemother. 1988 May;32(5):693-701. | |||||
REF 9 | 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. | |||||
REF 10 | Bactericidal effect of piperacillin alone and combined. Presse Med. 1986 Dec 20;15(46):2297-302. | |||||
REF 11 | Moxalactam (6059-S), a new 1-oxa-beta-lactam: binding affinity for penicillin-binding proteins of Escherichia coli K-12. | |||||
REF 12 | 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. | |||||
REF 13 | 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. | |||||
REF 14 | Microbiology, pharmacology, and clinical use of mezlocillin sodium. Pharmacotherapy. 1982 Nov-Dec;2(6):300-12. | |||||
REF 15 | DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41. | |||||
REF 16 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
REF 17 | Interaction Mode of the Novel Monobactam AIC499 Targeting Penicillin Binding Protein 3 of Gram-Negative Bacteria. Biomolecules. 2021 Jul 19;11(7):1057. |
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