Target Information
| Target General Information | Top | |||||
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| Target ID |
T02024
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| Target Name |
HUMAN inosine-5'-monophosphate dehydrogenase 1 (IMPDH1)
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| Synonyms |
Superoxide-inducible protein 12; SOI12; Probable inosine-5'-monophosphate dehydrogenase IMD1; NAD-dependent inosine monophosphate dehydrogenase; Inosine dehydrogenase; IMPDH-I; IMPDH 1; IMPDH; IMPD1; IMPD 1; IMPD; IMP dehydrogenase 1; IMP dehydrogenase
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| Gene Name |
IMPDH1
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| Disease | [+] 1 Target-related Diseases | + | ||||
| 1 | Hepatitis virus infection [ICD-11: 1E50-1E51] | |||||
| Function |
Catalyzes the conversion of inosine 5'-phosphate (IMP) to xanthosine 5'-phosphate (XMP), the first committed and rate-limiting step in the de novo synthesis of guanine nucleotides, and therefore plays an important role in the regulation of cell growth. Could also have a single-stranded nucleic acid-binding activity and could play a role in RNA and/or DNA metabolism. It may also have a role in the development of malignancy and the growth progression of some tumors.
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| BioChemical Class |
CH-OH donor oxidoreductase
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| UniProt ID | ||||||
| EC Number |
EC 1.1.1.205
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| Sequence |
MADYLISGGTGYVPEDGLTAQQLFASADGLTYNDFLILPGFIDFIADEVDLTSALTRKIT
LKTPLISSPMDTVTEADMAIAMALMGGIGFIHHNCTPEFQANEVRKVKKFEQGFITDPVV LSPSHTVGDVLEAKMRHGFSGIPITETGTMGSKLVGIVTSRDIDFLAEKDHTTLLSEVMT PRIELVVAPAGVTLKEANEILQRSKKGKLPIVNDCDELVAIIARTDLKKNRDYPLASKDS QKQLLCGAAVGTREDDKYRLDLLTQAGVDVIVLDSSQGNSVYQIAMVHYIKQKYPHLQVI GGNVVTAAQAKNLIDAGVDGLRVGMGCGSICITQEVMACGRPQGTAVYKVAEYARRFGVP IIADGGIQTVGHVVKALALGASTVMMGSLLAATTEAPGEYFFSDGVRLKKYRGMGSLDAM EKSSSSQKRYFSEGDKVKIAQGVSGSIQDKGSIQKFVPYLIAGIQHGCQDIGARSLSVLR SMMYSGELKFEKRTMSAQIEGGVHGLHSYEKRLY 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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| Drugs in Phase 1 Trial | [+] 1 | + | ||||
| 1 | Ribavirin | Drug Info | Approved | Hepatitis C virus infection | [2] | |
| Mode of Action | [+] 1 Modes of Action | + | ||||
| Inhibitor | [+] 1 Inhibitor drugs | + | ||||
| 1 | Ribavirin | Drug Info | [1] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Adenosine triphosphate | Ligand Info | |||||
| Structure Description | HUMAN IMPDH1 TREATED WITH GTP, IMP, AND NAD+; INTERFACE-CENTERED | PDB:7RFE | ||||
| Method | Electron microscopy | Resolution | 2.60 Å | Mutation | No | [3] |
| PDB Sequence |
GYVPEDGLTA
20 QQLFASADGL30 TYNDFLILPG40 FIDFIADEVD50 LTSALTRKIT60 LKTPLISSPM 70 DTVTEADMAI80 AMALMGGIGF90 IHHNCTPEFQ100 ANEVRKVKKF110 EQGFITDPVV 120 LSPSHTVGDV130 LEAKMRHGFS140 GIPITETGTM150 GSKLVGIVTS160 RDIVMTPRIE 184 LVVAPAGVTL194 KEANEILQRS204 KKGKLPIVND214 CDELVAIIAR224 TDLKKNRDYP 234 LASKDSQKQL244 LCGAAVGTRE254 DDKYRLDLLT264 QAGVDVIVLD274 SSQGNSVYQI 284 AMVHYIKQKY294 PHLQVIGGNV304 VTAAQAKNLI314 DAGVDGLRVG324 MGCGSICITQ 334 EVMACGRPQG344 TAVYKVAEYA354 RRFGVPIIAD364 GGIQTVGHVV374 KALALGASTV 384 MMGSLLAATT394 EAPGEYFFSD404 GVRLKKYRGM414 GSLDAMKVKI439 AQGVSGSIQD 449 KGSIQKFVPY459 LIAGIQHGCQ469 DIGARSLSVL479 RSMMYSGELK489 FEKRTMSAQI 499 EGGVHGLHSY509 EKRLY
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GLY141
4.838
ILE157
2.787
VAL158
3.407
THR159
2.298
SER160
1.689
ARG161
1.804
ASP162
1.670
MET179
4.618
THR180
1.770
GLU184
3.418
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: 6-Chloropurine Riboside, 5'-Monophosphate | Ligand Info | |||||
| Structure Description | BINARY COMPLEX OF HUMAN TYPE-I INOSINE MONOPHOSPHATE DEHYDROGENASE WITH 6-CL-IMP | PDB:1JCN | ||||
| Method | X-ray diffraction | Resolution | 2.50 Å | Mutation | No | [4] |
| PDB Sequence |
TGYVPEDGLT
19 AQQLFASADD29 LTYNDFLILP39 GFIDFIADEV49 DLTSALTRKI59 TLKTPLISSP 69 MDTVTEADMA79 IAMALMGGIG89 FIHHNCTPEF99 QANEVRKVKN109 FEQGFITDPV 119 VLSPGIPITE146 VGIVTSRDID164 PRIELVVAPA190 GVTLKEANEI200 LQRSKKGKLP 210 IVNDCDELVR224 TDLKKNRDYP234 LASKDSQKQL244 LCGAAVGTRE254 DDKYRLDLLT 264 QAGVDVIVLD274 SSQGNSVYQI284 AMVHYIKQKY294 PHLQVIGGNV304 VTAAQAKNLI 314 DAGVDGLRVG324 MGCGSICITQ334 EVMACGRPQG344 TAVYKVAEYA354 RRFGVPIIAD 364 GGIQTVGHVV374 KALALGASTV384 MMGSLLAATT394 EAPGEKGSIQ454 KFVPYLIAGI 464 QHGCQDIGAR474 SLSVLRSMMY484 SGELKFEKRT494 MSAQI
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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 Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Human Pathway Affiliation
of target is determined by the life-essential pathways provided on KEGG database. The target-affiliated pathways were defined based on the following two criteria (a) the pathways of the studied target should be life-essential for both healthy individuals and patients, and (b) the studied target should occupy an upstream position in the pathways and therefore had the ability to regulate biological function.
Targets involved in a fewer pathways have greater likelihood to be successfully developed, while those associated with more human pathways increase the chance of undesirable interferences with other human processes
(Pharmacol Rev, 58: 259-279, 2006).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Human Pathway Affiliation
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| KEGG Pathway | Pathway ID | Affiliated Target | Pathway Map |
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| Purine metabolism | hsa00230 | Affiliated Target |
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| Class: Metabolism => Nucleotide metabolism | Pathway Hierarchy | ||
| Drug metabolism - other enzymes | hsa00983 | Affiliated Target |
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| Class: Metabolism => Xenobiotics biodegradation and metabolism | Pathway Hierarchy | ||
| Degree | 4 | Degree centrality | 4.30E-04 | Betweenness centrality | 9.24E-06 |
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| Closeness centrality | 1.69E-01 | Radiality | 1.27E+01 | Clustering coefficient | 6.67E-01 |
| Neighborhood connectivity | 1.28E+01 | Topological coefficient | 3.98E-01 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Target Poor or Non Binders | Top | |||||
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| Target Poor or Non Binders | ||||||
| References | Top | |||||
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| REF 1 | Proteomics of SARS-CoV-2-infected Host Cells Reveals Therapy Targets. Nature. 2020 May 14. doi: 10.1038/s41586-020-2332-7. | |||||
| REF 2 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 3 | IMPDH1 retinal variants control filament architecture to tune allosteric regulation. Nat Struct Mol Biol. 2022 Jan;29(1):47-58. | |||||
| REF 4 | Crystal Structure of the Human Type I Inosine Monophosphate Dehydrogenase and Implications for Isoform Specificity | |||||
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