Target Information
| Target General Information | Top | |||||
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| Target ID |
T94400
(Former ID: TTDR00929)
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| Target Name |
Mycobacterium Thymidine monophosphate kinase (MycB tmk)
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| Synonyms |
tmk; Thymidylic kinase; Thymidylic acid kinase; Thymidylate monophosphate kinase; Thymidylate kinase; Thymidine 5'-monophosphate kinase; TMPK; Deoxythymidine 5'-monophosphate kinase; DTMPkinase
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| Gene Name |
MycB tmk
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| Target Type |
Literature-reported target
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| Function |
Catalyzes the reversible phosphorylation of deoxythymidine monophosphate (dTMP) to deoxythymidine diphosphate (dTDP), using ATP as its preferred phosphoryl donor. Situated at the junction of both de novo and salvage pathways of deoxythymidine triphosphate (dTTP) synthesis, is essential for DNA synthesis and cellular growth. Has a broad specificity for nucleoside triphosphates, being highly active withATP or dATP as phosphate donors, and less active with ITP, GTP, CTP and UTP.
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| BioChemical Class |
Kinase
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| UniProt ID | ||||||
| EC Number |
EC 2.7.4.9
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| Sequence |
MLIAIEGVDGAGKRTLVEKLSGAFRAAGRSVATLAFPRYGQSVAADIAAEALHGEHGDLA
SSVYAMATLFALDRAGAVHTIQGLCRGYDVVILDRYVASNAAYSAARLHENAAGKAAAWV QRIEFARLGLPKPDWQVLLAVSAELAGERSRGRAQRDPGRARDNYERDAELQQRTGAVYA ELAAQGWGGRWLVVGADVDPGRLAATLAPPDVPS 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 triphosphate | Ligand Info | |||||
| Structure Description | CRYSTAL STRUCTURE OF INACTIVE MYCOBACTERIUM TUBERCULOSIS THYMIDYLATE KINASE COMPLEXED WITH THYMIDINE MONOPHOSPHATE (TMP) AT PH 4.6 (RESOLUTION 1.85 A) | PDB:1N5I | ||||
| Method | X-ray diffraction | Resolution | 1.85 Å | Mutation | No | [7] |
| PDB Sequence |
MLIAIEGVDG
10 AGKRTLVEKL20 SGAFRAAGRS30 VATLAFPRYG40 QSVAADIAAE50 ALHGEHGDLA 60 SSVYAMATLF70 ALDRAGAVHT80 IQGLCRGYDV90 VILDRYVASN100 AAYSAARLHE 110 NAAGKAAAWV120 QRIEFARLGL130 PKPDWQVLLA140 VSAELAGERS150 RGRAQRDPGR 160 ARDNYERDAE170 LQQRTGAVYA180 ELAAQGWGGR190 WLVVGADVDP200 GRLAATLA |
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| Ligand Name: Thymidine-5'-Phosphate | Ligand Info | |||||
| Structure Description | CRYSTAL STRUCTURE OF MYCOBACTERIUM TUBERCULOSIS THYMIDYLATE KINASE COMPLEXED WITH THYMIDINE MONOPHOSPHATE (TMP) | PDB:1GSI | ||||
| Method | X-ray diffraction | Resolution | 1.60 Å | Mutation | No | [8] |
| PDB Sequence |
MLIAIEGVDG
10 AGKRTLVEKL20 SGAFRAAGRS30 VATLAFPRYG40 QSVAADIAAE50 ALHGEHGDLA 60 SSVYAMATLF70 ALDRAGAVHT80 IQGLCRGYDV90 VILDRYVASN100 AAYSAARLHE 110 NAAGKAAAWV120 QRIEFARLGL130 PKPDWQVLLA140 VSAELAGERS150 RGRAQRDPGR 160 ARDNYERDAE170 LQQRTGAVYA180 ELAAQGWGGR190 WLVVGADVDP200 GRLAATLA |
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| 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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| 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 Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| Target Affiliated Biological Pathways | Top | |||||
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| KEGG Pathway | [+] 2 KEGG Pathways | + | ||||
| 1 | Pyrimidine metabolism | |||||
| 2 | Metabolic pathways | |||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | Thymidylate kinase as target enzyme for 5'-deoxythymidine and various 5'-deoxy-5'-halogeno pyrimidine nucleosides. Acta Biol Med Ger. 1969;23(6):Suppl:K 19+. | |||||
| REF 2 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 3 | Rational design of 5'-thiourea-substituted alpha-thymidine analogues as thymidine monophosphate kinase inhibitors capable of inhibiting mycobacteri... J Med Chem. 2007 Nov 1;50(22):5281-92. | |||||
| REF 4 | The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. | |||||
| REF 5 | Substituted benzyl-pyrimidines targeting thymidine monophosphate kinase of Mycobacterium tuberculosis: synthesis and in vitro anti-mycobacterial ac... Bioorg Med Chem. 2008 Jun 1;16(11):6075-85. | |||||
| REF 6 | DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41. | |||||
| REF 7 | Mycobacterium tuberculosis thymidylate kinase: structural studies of intermediates along the reaction pathway. J Mol Biol. 2003 Apr 11;327(5):1077-92. | |||||
| REF 8 | Cryophotolysis of caged compounds: a technique for trapping intermediate states in protein crystals. Acta Crystallogr D Biol Crystallogr. 2002 Apr;58(Pt 4):607-14. | |||||
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