Target Information
| Target General Information | Top | |||||
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| Target ID |
T79724
(Former ID: TTDR00748)
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| Target Name |
Bacterial Hydroxymethyl-dihydropterin pyrophosphokinase (Bact folK)
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| Synonyms |
PPPK; HPPK; 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase; 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase; 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase
Click to Show/Hide
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| Gene Name |
Bact folK
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| Target Type |
Literature-reported target
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[1] | ||||
| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Schizophrenia [ICD-11: 6A20] | |||||
| Function |
2-amino-4-hydroxy-6-hydroxymethyldihydropteridine diphosphokinase activity, magnesium ion binding
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| BioChemical Class |
Kinase
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| UniProt ID | ||||||
| Sequence |
MTVAYIAIGSNLASPLEQVNAALKALGDIPESHILTVSSFYRTPPLGPQDQPDYLNAAVA
LETSLAPEELLNHTQRIELQQGRVRKAERWGPRTLDLDIMLFGNEVINTERLTVPHYDMK NRGFMLWPLFEIAPELVFPDGEMLRQILHTRAFDKLNKW Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| Drugs and Modes of Action | Top | |||||
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| Preclinical Drug(s) | [+] 1 Preclinical Drugs | + | ||||
| 1 | PD-157695 | Drug Info | Preclinical | Schizophrenia | [2] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 7 Inhibitor drugs | + | ||||
| 1 | PD-157695 | Drug Info | [1] | |||
| 2 | 6-Hydroxymethyl-7,8-Dihydropterin | Drug Info | [3] | |||
| 3 | 6-Hydroxymethylpterin | Drug Info | [4] | |||
| 4 | Acetate Ion | Drug Info | [3] | |||
| 5 | P(1)-(6-Hydroxymethylpterin)-P(4)-(5'-adenosyl)tetraphosphate | Drug Info | [1] | |||
| 6 | [3H]alphabeta-meATP | Drug Info | [3] | |||
| 7 | [Pterin-6-Yl Methanyl]-Phosphonophosphate | Drug Info | [3] | |||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Adenosine monophosphate | Ligand Info | |||||
| Structure Description | CRYSTAL STRUCTURE OF A TERNARY COMPLEX OF E. COLI HPPK WITH AMP AND 6-HYDROXYMETHYLPTERIN-DIPHOSPHATE AT 1.56 ANGSTROM RESOLUTION | PDB:1RAO | ||||
| Method | X-ray diffraction | Resolution | 1.56 Å | Mutation | No | [5] |
| PDB Sequence |
TVAYIAIGSN
10 LASPLEQVNA20 ALKALGDIPE30 SHILTVSSFY40 RTPPLGPQDQ50 PDYLNAAVAL 60 ETSLAPEELL70 NHTQRIELQQ80 GRVRKAERWG90 PRTLDLDIML100 FGNEVINTER 110 LTVPHYDMKN120 RGFMLWPLFE130 IAPELVFPDG140 EMLRQILHTR150 AFDKLNKW |
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| Ligand Name: Thioguanine | Ligand Info | |||||
| Structure Description | The Identification, Analysis and Structure-Based Development of Novel Inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase | PDB:4M5M | ||||
| Method | X-ray diffraction | Resolution | 1.12 Å | Mutation | No | [6] |
| PDB Sequence |
MTVAYIAIGS
9 NLASPLEQVN19 AALKALGDIP29 ESHILTVSSF39 YRTPPLGPQD49 QPDYLNAAVA 59 LETSLAPEEL69 LNHTQRIELQ79 QGRVRKAERW89 GPRTLDLDIM99 LFGNEVINTE 109 RLTVPHYDMK119 NRGFMLWPLF129 EIAPELVFPD139 GEMLRQILHT149 RAFDKLNKW |
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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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| 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 | ||||||
| References | Top | |||||
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| REF 1 | Bisubstrate analogue inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase: synthesis and biochemical and crystallographic studies. J Med Chem. 2001 Apr 26;44(9):1364-71. | |||||
| REF 2 | The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22. | |||||
| REF 3 | How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6. | |||||
| REF 4 | DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41. | |||||
| REF 5 | Reaction trajectory of pyrophosphoryl transfer catalyzed by 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase. Structure. 2004 Mar;12(3):467-75. | |||||
| REF 6 | The identification, analysis and structure-based development of novel inhibitors of 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase. Bioorg Med Chem. 2014 Apr 1;22(7):2157-65. | |||||
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