Target Information
| Target General Information | Top | |||||
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| Target ID |
T02228
(Former ID: TTDS00084)
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| Target Name |
Streptococcus Topoisomerase IV A (Stre-coc parC)
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| Synonyms |
parC of Streptococcus pneumoniae serotype 4; DNA topoisomerase IV of Streptococcus pneumoniae serotype 4
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| Gene Name |
Stre-coc parC
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Otitis externa [ICD-11: AA00-AA13] | |||||
| Function |
Topoisomerase IV is essential for chromosome segregation. It relaxes supercoiled DNA. Performs the decatenation events required during the replication of a circular DNA molecule.
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| BioChemical Class |
Topoisomerase GyrA ParC
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| UniProt ID | ||||||
| EC Number |
EC 5.6.2.3
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| Sequence |
MSNIQNMSLEDIMGERFGRYSKYIIQDRALPDIRDGLKPVQRRILYSMNKDSNTFDKSYR
KSAKSVGNIMGNFHPHGDSSIYDAMVRMSQNWKNREILVEMHGNNGSMDGDPPAAMRYTE ARLSEIAGYLLQDIEKKTVPFAWNFDDTEKEPTVLPAAFPNLLVNGSTGISAGYATDIPP HNLAEVIDAAVYMIDHPTAKIDKLMEFLPGPDFPTGAIIQGRDEIKKAYETGKGRVVVRS KTEIEKLKGGKEQIVIIEIPYEINKANLVKKIDDVRVNNKVAGIAEVRDESDRDGLRIAI ELKKDANTELVLNYLFKYTDLQINYNFNMVAIDNFTPRQVGIVPILSSYIAHRREVILAR SRFDKEKAEKRLHIVEGLIRVISILDEVIALIRASENKADAKENLKVSYDFTEEQAEAIV TLQLYRLTNTDVVVLQEEEAELREKIAMLAAIIGDERTMYNLMKKELREVKKKFATPRLS SLEDTAKAIEIDTASLIAEEDTYVSVTKAGYIKRTSPRSFAASTLEEIGKRDDDRLIFVQ SAKTTQHLLMFTSLGNVIYRPIHELADIRWKDIGEHLSQTITNFETNEEILYVEVLDQFD DATTYFAVTRLGQIKRVERKEFTPWRTYRSKSVKYAKLKDDTDQIVAVAPIKLDDVVLVS QNGYALRFNIEEVPVVGAKAAGVKAMNLKEDDVLQSGFICNTSSFYLLTQRGSLKRVSIE EILATSRAKRGLQVLRELKNKPHRVFLAGAVAEQGFVGDFFSTEVDVNDQTLLVQSNKGT IYESRLQDLNLSERTSNGSFISDTISDEEVFDAYLQEVVTEDK Click to Show/Hide
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| Drugs and Modes of Action | Top | |||||
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| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | Cetraxal Otic | Drug Info | Phase 3 | Otitis externa | [1], [2] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | Cetraxal Otic | Drug Info | [1], [2], [3] | |||
| Inhibitor | [+] 2 Inhibitor drugs | + | ||||
| 1 | Premafloxacin | Drug Info | [4] | |||
| 2 | Pumiliotoxin 251D | Drug Info | [5] | |||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Levofloxacin | Ligand Info | |||||
| Structure Description | Detailed structural insight into the quinolone-DNA cleavage complex of type IIA topoisomerases | PDB:3K9F | ||||
| Method | X-ray diffraction | Resolution | 2.90 Å | Mutation | No | [6] |
| PDB Sequence |
NIQNMSLEDI
12 MGERFGRYSK22 YIIQDRALPD32 IRDGLKPVQR42 RILYSMNKDS52 NTFDKSYRKS 62 AKSVGNIMGN72 FHPHGDSSIY82 DAMVRMSQNW92 KNREILVEMH102 GNNGSMDGDP 112 PAAMRYTEAR122 LSEIAGYLLQ132 DIEKKTVPFA142 WNFDDTEKEP152 TVLPAAFPNL 162 LVNGSTGISA172 GYATDIPPHN182 LAEVIDAAVY192 MIDHPTAKID202 KLMEFLPGPD 212 FPTGAIIQGR222 DEIKKAYETG232 KGRVVVRSKT242 EIEKLKGGKE252 QIVITEIPYE 262 INKANLVKKI272 DDVRVNNKVA282 GIAEVRDESD292 RDGLRIAIEL302 KKDANTELVL 312 NYLFKYTDLQ322 INYNFNMVAI332 DNFTPRQVGI342 VPILSSYIAH352 RREVILARSR 362 FDKEKAEKRL372 HIVEGLIRVI382 SILDEVIALI392 RASENKADAK402 ENLKVSYDFT 412 EEQAEAIVTL422 QLYRLTNTDV432 VVLQEEEAEL442 REKIAMLAAI452 IGDERTMYNL 462 MKKELREVKK472 KFATPRLSSL482 E
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Trovafloxacin | Ligand Info | |||||
| Structure Description | Quinolone(Trovafloxacin)-DNA cleavage complex of type IV topoisomerase from S. pneumoniae | PDB:4KOE | ||||
| Method | X-ray diffraction | Resolution | 3.02 Å | Mutation | Yes | [7] |
| PDB Sequence |
NIQNMSLEDI
12 MGERFGRYSK22 YIIQDRALPD32 IRDGLKPVQR42 RILYSMNKDS52 NTFDKSYRKS 62 AKSVGNIMGN72 FHPHGDSSIY82 DAMVRMSQNW92 KNREILVEMH102 GNNGSMDGDP 112 PAAMRYTEAR122 LSEIAGYLLQ132 DIEKKTVPFA142 WNFDDTEKEP152 TVLPAAFPNL 162 LVNGSTGISA172 GYATDIPPHN182 LAEVIDAAVY192 MIDHPTAKID202 KLMEFLPGPD 212 FPTGAIIQGR222 DEIKKAYETG232 KGRVVVRSKT242 EIEKLKGGKE252 QIVITEIPYE 262 INKANLVKKI272 DDVRVNNKVA282 GIAEVRDESD292 RDGLRIAIEL302 KKDANTELVL 312 NYLFKYTDLQ322 INYNFNMVAI332 DNFTPRQVGI342 VPILSSYIAH352 RREVILARSR 362 FDKEKAEKRL372 HIVEGLIRVI382 SILDEVIALI392 RASENKADAK402 ENLKVSYDFT 412 EEQAEAIVTL422 QLYRLTNTDV432 VVLQEEEAEL442 REKIAMLAAI452 IGDERTMYNL 462 MKKELREVKK472 KFATPRLSSL482 ED
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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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| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. Chem Biol. 2010 May 28;17(5):421-33. | |||||
| REF 2 | DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol Mol Biol Rev. 1997 Sep;61(3):377-92. | |||||
| REF 3 | Selective Targeting of Topoisomerase IV and DNA Gyrase in Staphylococcus aureus: Different Patterns of Quinolone- Induced Inhibition of DNA Synthesis. Antimicrob Agents Chemother. 2000 August; 44(8):2160-2165. | |||||
| REF 4 | Alteration of Escherichia coli topoisomerase IV to novobiocin resistance. Antimicrob Agents Chemother. 2003 Mar;47(3):941-7. | |||||
| REF 5 | How many modes of action should an antibiotic have Curr Opin Pharmacol. 2008 Oct;8(5):564-73. | |||||
| REF 6 | Structural basis of gate-DNA breakage and resealing by type II topoisomerases. PLoS One. 2010 Jun 28;5(6):e11338. | |||||
| REF 7 | Quinolone(Trovafloxacin)-DNA cleavage complex of type IV topoisomerase from S. pneumoniae | |||||
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