Target Information
| Target General Information | Top | |||||
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| Target ID |
T02584
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| Target Name |
Mycobacterium Leucine-tRNA ligase (MycB leuS)
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| Synonyms |
Leucyl-tRNA synthetase; LeuRS
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| Gene Name |
MycB leuS
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| Target Type |
Clinical trial target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | HIV-infected patients with tuberculosis [ICD-11: 1B10-1B14] | |||||
| UniProt ID | ||||||
| EC Number |
EC 6.1.1.4
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| Sequence |
MTESPTAGPGGVPRADDADSDVPRYRYTAELAARLERTWQENWARLGTFNVPNPVGSLAP
PDGAAVPDDKLFVQDMFPYPSGEGLHVGHPLGYIATDVYARYFRMVGRNVLHALGFDAFG LPAEQYAVQTGTHPRTRTEANVVNFRRQLGRLGFGHDSRRSFSTTDVDFYRWTQWIFLQI YNAWFDTTANKARPISELVAEFESGARCLDGGRDWAKLTAGERADVIDEYRLVYRADSLV NWCPGLGTVLANEEVTADGRSDRGNFPVFRKRLRQWMMRITAYADRLLDDLDVLDWPEQV KTMQRNWIGRSTGAVALFSARAASDDGFEVDIEVFTTRPDTLFGATYLVLAPEHDLVDEL VAASWPAGVNPLWTYGGGTPGEAIAAYRRAIAAKSDLERQESREKTGVFLGSYAINPANG EPVPIFIADYVLAGYGTGAIMAVPGHDQRDWDFARAFGLPIVEVIAGGNISESAYTGDGI LVNSDYLNGMSVPAAKRAIVDRLESAGRGRARIEFKLRDWLFARQRYWGEPFPIVYDSDG RPHALDEAALPVELPDVPDYSPVLFDPDDADSEPSPPLAKATEWVHVDLDLGDGLKPYSR DTNVMPQWAGSSWYELRYTDPHNSERFCAKENEAYWMGPRPAEHGPDDPGGVDLYVGGAE HAVLHLLYSRFWHKVLYDLGHVSSREPYRRLVNQGYIQAYAYTDARGSYVPAEQVIERGD RFVYPGPDGEVEVFQEFGKIGKSLKNSVSPDEICDAYGADTLRVYEMSMGPLEASRPWAT KDVVGAYRFLQRVWRLVVDEHTGETRVADGVELDIDTLRALHRTIVGVSEDFAALRNNTA TAKLIEYTNHLTKKHRDAVPRAAVEPLVQMLAPLAPHIAEELWLRLGNTTSLAHGPFPKA DAAYLVDETVEYPVQVNGKVRGRVVVAADTDEETLKAAVLTDEKVQAFLAGATPRKVIVV AGRLVNLVI 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 | GSK3036656 | Drug Info | Phase 2 | Tuberculosis | [2] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | GSK3036656 | Drug Info | [1] | |||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: [(1R,3S,5S,6R,8R,9'S)-9'-(aminomethyl)-8-(6-aminopurin-9-yl)-5'-ethoxyspiro[2,4,7-trioxa-3-boranuidabicyclo[3.3.0]octane-3,7'-8-oxa-7-boranuidabicyclo[4.3.0]nona-1(6),2,4-triene]-6-yl]methyl phosphate | Ligand Info | |||||
| Structure Description | Crystal structure of the LeuRS editing domain of Mycobacterium tuberculosis in complex with the adduct (S)-3-(Aminomethyl)-7-ethoxybenzo[c][1,2]oxaborol-1(3H)-ol-AMP | PDB:5AGR | ||||
| Method | X-ray diffraction | Resolution | 1.30 Å | Mutation | No | [3] |
| PDB Sequence |
GAVALFSARA
322 VDIEVFTTRP339 DTLFGATYLV349 LAPEHDLVDE359 LVAASWPAGV369 NPLWTYGGGT 379 PGEAIAAYRR389 AIAAKSDLER399 QKTGVFLGSY413 AINPANGEPV423 PIFIADYVLA 433 GYGTGAIMAV443 PGHDQRDWDF453 ARAFGLPIVE463 VIAGGNISES473 AYTGDGILVN 483 SDYLNGMSVP493 AAKRAIVDRL503 ESAGRGRARI513
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PHE335
3.590
THR336
2.742
THR337
2.903
ARG338
3.521
THR341
4.488
TYR430
3.510
VAL431
3.523
LEU432
2.846
TYR435
2.409
GLY436
4.644
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| Ligand Name: [(1R,3S,5S,6R,8R,9'S)-9'-(aminomethyl)-8-(6-aminopurin-9-yl)-2'-chloro-5'-ethoxyspiro[2,4,7-trioxa-3-boranuidabicyclo[3.3.0]octane-3,7'-8-oxa-7-boranuidabicyclo[4.3.0]nona-1,3,5-triene]-6-yl]methyl phosphate | Ligand Info | |||||
| Structure Description | Crystal structure of the LeuRS editing domain of Mycobacterium tuberculosis in complex with the adduct (S)-3-(Aminomethyl)-4-chloro-7-ethoxybenzo[c][1,2]oxaborol-1(3H)-ol-AMP | PDB:5AGT | ||||
| Method | X-ray diffraction | Resolution | 1.45 Å | Mutation | No | [3] |
| PDB Sequence |
GAVALFSARA
322 VDIEVFTTRP339 DTLFGATYLV349 LAPEHDLVDE359 LVAASWPAGV369 NPLWTYGGGT 379 PGEAIAAYRR389 AIAAKSDLER399 QKTGVFLGSY413 AINPANGEPV423 PIFIADYVLA 433 GYGTGAIMAV443 PGHDQRDWDF453 ARAFGLPIVE463 VIAGGNISES473 AYTGDGILVN 483 SDYLNGMSVP493 AAKRAIVDRL503 ESAGRGRARI513
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PHE335
3.649
THR336
2.697
THR337
2.942
ARG338
3.489
THR341
3.555
TYR430
3.562
VAL431
3.558
LEU432
2.828
TYR435
2.455
GLY436
4.540
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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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| References | Top | |||||
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| REF 1 | Discovery of a Potent and Specific M. tuberculosis Leucyl-tRNA Synthetase Inhibitor: (S)-3-(Aminomethyl)-4-chloro-7-(2-hydroxyethoxy)benzo[c][1,2]oxaborol-1(3H)-ol (GSK656). J Med Chem. 2017 Oct 12;60(19):8011-8026. | |||||
| REF 2 | ClinicalTrials.gov (NCT03557281) An Early Bactericidal Activity, Safety and Tolerability of GSK3036656 in Subjects With Drug-sensitive Pulmonary Tuberculosis. U.S. National Institutes of Health. | |||||
| REF 3 | Discovery of Novel Oral Protein Synthesis Inhibitors of Mycobacterium tuberculosis That Target Leucyl-tRNA Synthetase. Antimicrob Agents Chemother. 2016 Sep 23;60(10):6271-80. | |||||
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