Target Information
| Target General Information | Top | |||||
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| Target ID |
T70310
(Former ID: TTDR00898)
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| Target Name |
Bacterial DNA ligase (Bact ligA)
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| Synonyms |
ligA; Polydeoxyribonucleotide synthase [NAD+]; NAD+-dependent DNA ligase
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| Gene Name |
Bact ligA
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| Target Type |
Literature-reported target
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[1] | ||||
| Function |
DNA ligase that catalyzes the formation of phosphodiester linkages between 5'-phosphoryl and 3'-hydroxyl groups in double-stranded DNA using NAD as a coenzyme and as the energy source for the reaction. It is essential for DNA replication and repair of damaged DNA.
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| BioChemical Class |
Phosphoric ester ligase
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| UniProt ID | ||||||
| EC Number |
EC 6.5.1.2
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| Sequence |
MESIEQQLTELRTTLRHHEYLYHVMDAPEIPDAEYDRLMRELRELETKHPELITPDSPTQ
RVGAAPLAAFSQIRHEVPMLSLDNVFDEESFLAFNKRVQDRLKNNEKVTWCCELKLDGLA VSILYENGVLVSAATRGDGTTGEDITSNVRTIRAIPLKLHGENIPARLEVRGEVFLPQAG FEKINEDARRTGGKVFANPRNAAAGSLRQLDPRITAKRPLTFFCYGVGVLEGGELPDTHL GRLLQFKKWGLPVSDRVTLCESAEEVLAFYHKVEEDRPTLGFDIDGVVIKVNSLAQQEQL GFVARAPRWAVAFKFPAQEQMTFVRDVEFQVGRTGAITPVARLEPVHVAGVLVSNATLHN ADEIERLGLRIGDKVVIRRAGDVIPQVVNVVLSERPEDTREVVFPTHCPVCGSDVERVEG EAVARCTGGLICGAQRKESLKHFVSRRAMDVDGMGDKIIDQLVEKEYVHTPADLFKLTAG KLTGLERMGPKSAQNVVNALEKAKETTFARFLYALGIREVGEATAAGLAAYFGTLEALEA ASIEELQKVPDVGIVVASHVHNFFAEESNRNVISELLAEGVHWPAPIVINAEEIDSPFAG KTVVLTGSLSQMSRDDAKARLVELGAKVAGSVSKKTDLVIAGEAAGSKLAKAQELGIEVI DEAEMLRLLGS Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Adenosine monophosphate | Ligand Info | |||||
| Structure Description | Last Stop on the Road to Repair: Structure of E.coli DNA Ligase Bound to Nicked DNA-Adenylate | PDB:2OWO | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [2] |
| PDB Sequence |
MESIEQQLTE
10 LRTTLRHHEY20 LYHVMDAPEI30 PDAEYDRLMR40 ELRELETKHP50 ELITPDSPTQ 60 RVGAAPLAAF70 SQIRHEVPML80 SLDNVFDEES90 FLAFNKRVQD100 RLKNNEKVTW 110 CCELKLDGLA120 VSILYENGVL130 VSAATRGDGT140 TGEDITSNVR150 TIRAIPLKLH 160 GENIPARLEV170 RGEVFLPQAG180 FEKINEDARR190 TGGKVFANPR200 NAAAGSLRQL 210 DPRITAKRPL220 TFFCYGVGVL230 EGGELPDTHL240 GRLLQFKKWG250 LPVSDRVTLC 260 ESAEEVLAFY270 HKVEEDRPTL280 GFDIDGVVIK290 VNSLAQQEQL300 GFVARAPRWA 310 VAFKFPAQEQ320 MTFVRDVEFQ330 VGRTGAITPV340 ARLEPVHVAG350 VLVSNATLHN 360 ADEIERLGLR370 IGDKVVIRRA380 GDVIPQVVNV390 VLSERPEDTR400 EVVFPTHCPV 410 CGSDVERVEG420 EAVARCTGGL430 ICGAQRKESL440 KHFVSRRAMD450 VDGMGDKIID 460 QLVEKEYVHT470 PADLFKLTAG480 KLTGLERMGP490 KSAQNVVNAL500 EKAKETTFAR 510 FLYALGIREV520 GEATAAGLAA530 YFGTLEALEA540 ASIEELQKVP550 DVGIVVASHV 560 HNFFAEESNR570 NVISELLAEG580 VHWPAP
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| Ligand Name: Nicotinamide-Adenine-Dinucleotide | Ligand Info | |||||
| Structure Description | Escherichia coli LigA (K115M) in complex with NAD+ | PDB:5TT5 | ||||
| Method | X-ray diffraction | Resolution | 1.55 Å | Mutation | Yes | [3] |
| PDB Sequence |
MESIEQQLTE
10 LRTTLRHHEY20 LYHVMDAPEI30 PDAEYDRLMR40 ELRELETKHP50 ELITPDSPTQ 60 RVGAAPLAAF70 SQIRHEVPML80 SLDNVFDEES90 FLAFNKRVQD100 RLVTWCCELM 115 LDGLAVSILY125 ENGVLVSAAT135 RGDGTTGEDI145 TSNVRTIRAI155 PLKLHGENIP 165 ARLEVRGEVF175 LPQAGFEKIN185 EDARRTGGKV195 FANPRNAAAG205 SLRQLDPRIT 215 AKRPLTFFCY225 GVGVLEGGEL235 PDTHLGRLLQ245 FKKWGLPVSD255 RVTLCESAEE 265 VLAFYHKVEE275 DRPTLGFDID285 GVVIKVNSLA295 QQEQLGFVAR305 APRWAVAFKF 315 PAQEQMTFVR325 DVEFQVGRTG335 AITPVARLEP345 VHVAGVLVSN355 ATLHNADEIE 365 RLGLRIGDKV375 VIRRAGDVIP385 QVVNVVLSER395 PEDTREVVFP405 THCPVCGSDV 415 ERVEGEAVAR425 CTGGLICGAQ435 RKESLKHFVS445 RRAMDVDGMG455 DKIIDQLVEK 465 EYVHTPADLF475 KLTAGKLTGL485 ERMGPKSAQN495 VVNALEKAKE505 TTFARFLYAL 515 GIREVGEATA525 AGLAAYFGTL535 EALEAASIEE545 LQKVPDVGIV555 VASHVHNFFA 565 EESNRNVISE575 LLAEGVHWPA585 P
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HIS18
3.414
GLU19
3.974
TYR22
3.306
HIS23
3.618
PRO28
3.571
GLU29
4.983
ILE30
2.971
PRO31
3.710
ASP32
3.064
ALA33
4.813
TYR35
3.423
ASP36
2.898
LEU80
3.649
SER81
2.671
LEU82
3.612
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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 | Identification and validation of human DNA ligase inhibitors using computer-aided drug design. J Med Chem. 2008 Aug 14;51(15):4553-62. | |||||
| REF 2 | Last stop on the road to repair: structure of E. coli DNA ligase bound to nicked DNA-adenylate. Mol Cell. 2007 Apr 27;26(2):257-71. | |||||
| REF 3 | Two-metal versus one-metal mechanisms of lysine adenylylation by ATP-dependent and NAD(+)-dependent polynucleotide ligases. Proc Natl Acad Sci U S A. 2017 Mar 7;114(10):2592-2597. | |||||
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