Target Information
| Target General Information | Top | |||||
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| Target ID |
T81503
(Former ID: TTDR00228)
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| Target Name |
Bacterial DNA gyrase B (Bact gyrB)
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| Synonyms |
gyrB; DNA gyrase subunit B
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| Gene Name |
Bact gyrB
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Mycobacterium infection [ICD-11: 1B10-1B21] | |||||
| Function |
DNA gyrase negatively supercoils closed circular double- stranded DNA in an ATP-dependent manner and also catalyzes the interconversion of other topological isomers of double-stranded DNA rings, including catenanes and knotted rings.
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| BioChemical Class |
ATP-hydrolyzing DNA topoisomerase
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| UniProt ID | ||||||
| EC Number |
EC 5.6.2.3
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| Sequence |
MSNSYDSSSIKVLKGLDAVRKRPGMYIGDTDDGTGLHHMVFEVVDNAIDEALAGHCKEII
VTIHADNSVSVQDDGRGIPTGIHPEEGVSAAEVIMTVLHAGGKFDDNSYKVSGGLHGVGV SVVNALSQKLELVIQREGKIHRQIYEHGVPQAPLAVTGETEKTGTMVRFWPSLETFTNVT EFEYEILAKRLRELSFLNSGVSIRLRDKRDGKEDHFHYEGGIKAFVEYLNKNKTPIHPNI FYFSTEKDGIGVEVALQWNDGFQENIYCFTNNIPQRDGGTHLAGFRAAMTRTLNAYMDKE GYSKKAKVSATGDDAREGLIAVVSVKVPDPKFSSQTKDKLVSSEVKSAVEQQMNELLAEY LLENPTDAKIVVGKIIDAARAREAARRAREMTRRKGALDLAGLPGKLADCQERDPALSEL YLVEGDSAGGSAKQGRNRKNQAILPLKGKILNVEKARFDKMLSSQEVATLITALGCGIGR DEYNPDKLRYHSIIIMTDADVDGSHIRTLLLTFFYRQMPEIVERGHVYIAQPPLYKVKKG KQEQYIKDDEAMDQYQISIALDGATLHTNASAPALAGEALEKLVSEYNATQKMINRMERR YPKAMLKELIYQPTLTEADLSDEQTVTRWVNALVSELNDKEQHGSQWKFDVHTNAEQNLF EPIVRVRTHGVDTDYPLDHEFITGGEYRRICTLGEKLRGLLEEDAFIERGERRQPVASFE QALDWLVKESRRGLSIQRYKGLGEMNPEQLWETTMDPESRRMLRVTVKDAIAADQLFTTL MGDAVEPRRAFIEENALKAANIDI Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T01FVG | |||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Novobiocin | Ligand Info | |||||
| Structure Description | NOVOBIOCIN-RESISTANT MUTANT (R136H) OF THE N-TERMINAL 24 KDA FRAGMENT OF DNA GYRASE B COMPLEXED WITH NOVOBIOCIN AT 2.3 ANGSTROMS RESOLUTION | PDB:1AJ6 | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | Yes | [4] |
| PDB Sequence |
VLKGLDAVRK
21 RPGMYIGDTD31 DGTGLHHMVF41 EVVDNAIDEA51 LAGHCKEIIV61 TIHADNSVSV 71 QDDGRGIPTG81 IVSAAEVIMT96 VLHAGGKFSG113 GLHGVGVSVV123 NALSQKLELV 133 IQHEGKIHRQ143 IYEHGVPQAP153 LAVTGETEKT163 GTMVRFWPSL173 ETFTNVTEFE 183 YEILAKRLRE193 LSFLNSGVSI203 RLRDKRDGKE213 DHFH
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| Ligand Name: Salicylamide | Ligand Info | |||||
| Structure Description | E. coli GyrB ATPase domain in complex with 2-hydroxybenzamide | PDB:7DQH | ||||
| Method | X-ray diffraction | Resolution | 1.91 Å | Mutation | No | [5] |
| PDB Sequence |
LDAVRKRPGM
25 YIGDTDDGTG35 LHHMVFEVVD45 NAIDEALAGH55 CKEIIVTIHA65 DNSVSVQDDG 75 RGIPTGIHPE85 EGVSAAEVIM95 TVLGVGVSVV123 NALSQKLELV133 IQREGKIHRQ 143 IYEHGVPQAP153 LAVTGETEKT163 GTMVRFWPSL173 ETFTNVTEFE183 YEILAKRLRE 193 LSFLNSGVSI203 RLRDKRDGKE213 DHFHY
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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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| Chemical Structure based Activity Landscape of Target | Top |
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| Target Profiles in Patients | Top | |||||
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| Drug Resistance Mutation (DRM) | ||||||
| References | Top | |||||
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| REF 1 | Isolation and characterization of an Escherichia coli strain exhibiting partial tolerance to quinolones. Antimicrob Agents Chemother. 1989 May;33(5):705-9. | |||||
| REF 2 | ClinicalTrials.gov (NCT04553406) Phase 2a Safety, Tolerability, Pharmacokinetics and Efficacy of SPR720 for the Treatment of Patients With Mycobacterium Avium Complex (MAC) Pulmonary Disease. U.S. National Institutes of Health. | |||||
| REF 3 | seco-Cyclothialidines: new concise synthesis, inhibitory activity toward bacterial and human DNA topoisomerases, and antibacterial properties. J Med Chem. 2001 Feb 15;44(4):619-26. | |||||
| REF 4 | The entropic penalty of ordered water accounts for weaker binding of the antibiotic novobiocin to a resistant mutant of DNA gyrase: a thermodynamic and crystallographic study. Biochemistry. 1997 Aug 12;36(32):9663-73. | |||||
| REF 5 | Identification of new building blocks by fragment screening for discovering GyrB inhibitors. Bioorg Chem. 2021 Sep;114:105040. | |||||
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