Details of Drug-Metabolizing Enzyme (DME)

General Information of Drug-Metabolizing Enzyme (DME) (ID: DE2WSAL)

DME Name Purine nucleoside phosphorylase (PNP)
Synonyms Inosine-guanosine phosphorylase; Inosine phosphorylase; NP; PNP
Gene Name PNP
UniProt ID
PNPH_HUMAN
INTEDE ID
DME0437
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Gene ID
4860
EC Number EC: 2.4.2.1
Transferase
Glycosyltransferases
Pentosyltransferase
EC: 2.4.2.1
Lineage Species: Homo sapiens
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
Sequence
MENGYTYEDYKNTAEWLLSHTKHRPQVAIICGSGLGGLTDKLTQAQIFDYGEIPNFPRST
VPGHAGRLVFGFLNGRACVMMQGRFHMYEGYPLWKVTFPVRVFHLLGVDTLVVTNAAGGL
NPKFEVGDIMLIRDHINLPGFSGQNPLRGPNDERFGDRFPAMSDAYDRTMRQRALSTWKQ
MGEQRELQEGTYVMVAGPSFETVAECRVLQKLGADAVGMSTVPEVIVARHCGLRVFGFSL
ITNKVIMDYESLEKANHEEVLAAGKQAAQKLEQFVSILMASIPLPDKAS
Function
This enzyme catalyzes the phosphorolytic breakdown of the N-glycosidic bond in the beta-(deoxy)ribonucleoside molecules, with the formation of the corresponding free purine bases and pentose-1-phosphate.
KEGG Pathway
Metabolic pathways (hsa01100 )
Nicotinate and nicotinamide metabolism (hsa00760 )
Purine metabolism (hsa00230 )
Pyrimidine metabolism (hsa00240 )
Reactome Pathway
Purine catabolism (R-HSA-74259 )
Purine salvage (R-HSA-74217 )
Neutrophil degranulation (R-HSA-6798695 )

Molecular Interaction Atlas (MIA) of This DME

Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This DME
1 Approved Drug(s) Metabolized by This DME
Drug Name Drug ID Indication ICD 11 Highest Status REF
Ribavirin DMEYLH9 Hepatitis C virus infection 1E51.1 Approved [15]

Molecular Expression Atlas (MEA) of This DME

Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This DME
Disease Name ICD 11 Studied Tissue p-value Fold-Change Z-score
Acute myelocytic leukaemia 2B33.1 Bone marrow 2.78E-10 -4.40E-01 -7.27E-01
Alopecia ED70 Skin from scalp 1.45E-02 -1.21E-01 -3.94E-01
Alzheimer's disease 8A20 Entorhinal cortex 1.55E-04 3.57E-01 5.21E-01
Ankylosing spondylitis FA92.0 Pheripheral blood 7.59E-01 1.27E-02 3.57E-02
Aortic stenosis BB70 Calcified aortic valve 6.65E-01 9.55E-02 7.03E-02
Apnea 7A40 Hyperplastic tonsil 1.24E-01 -4.03E-01 -7.16E-01
Arthropathy FA00-FA5Z Peripheral blood 2.60E-01 -1.67E-01 -8.70E-01
Asthma CA23 Nasal and bronchial airway 6.42E-09 4.67E-01 4.86E-01
Atopic dermatitis EA80 Skin 7.91E-06 6.33E-01 1.77E+00
Autism 6A02 Whole blood 7.69E-02 -1.30E-01 -3.79E-01
Autoimmune uveitis 9A96 Peripheral monocyte 7.51E-01 -4.39E-01 -3.14E-01
Autosomal dominant monocytopenia 4B04 Whole blood 8.07E-03 2.32E+00 1.60E+00
Bacterial infection of gingival 1C1H Gingival tissue 8.21E-01 2.84E-02 7.36E-02
Batten disease 5C56.1 Whole blood 7.72E-01 -7.62E-02 -2.22E-01
Behcet's disease 4A62 Peripheral blood 2.69E-02 3.70E-01 1.20E+00
Bipolar disorder 6A60-6A6Z Prefrontal cortex 3.98E-01 1.18E-01 2.13E-01
Bladder cancer 2C94 Bladder tissue 2.23E-06 7.95E-01 3.13E+00
Breast cancer 2C60-2C6Z Breast tissue 4.71E-83 1.06E+00 1.56E+00
Cardioembolic stroke 8B11.20 Whole blood 2.32E-01 -3.54E-01 -9.90E-01
Cervical cancer 2C77 Cervical tissue 9.89E-01 -1.24E-02 -2.32E-02
Childhood onset rheumatic disease FA20.Z Peripheral blood 1.01E-01 3.54E-01 2.32E-01
Chronic hepatitis C 1E51.1 Whole blood 4.68E-01 1.80E-01 2.45E-01
Chronic obstructive pulmonary disease CA22 Lung tissue 6.41E-01 1.09E-01 1.23E-01
Chronic obstructive pulmonary disease CA22 Small airway epithelium 5.32E-06 5.07E-01 1.10E+00
Chronic rhinosinusitis CA0A Sinus mucosa tissue 7.38E-01 1.79E-01 3.95E-01
Colon cancer 2B90 Colon tissue 2.10E-01 1.29E-01 2.22E-01
Coronary artery disease BA80-BA8Z Peripheral blood 7.37E-02 8.77E-01 1.83E+00
Diffuse large B-cell lymphoma 2A81 Tonsil tissue 1.03E-01 3.64E-01 8.38E-01
Endometriosis GA10 Endometrium tissue 1.61E-01 3.95E-02 5.08E-02
Familial hypercholesterolemia 5C80.00 Peripheral blood 5.64E-04 2.65E-01 1.16E+00
Familial hypercholesterolemia 5C80.00 Whole blood 1.26E-04 3.35E-01 8.57E-01
Gastric cancer 2B72 Gastric tissue 5.73E-01 2.50E-01 1.93E-01
Glioblastopma 2A00.00 Nervous tissue 3.95E-69 1.01E+00 1.30E+00
Glioma 2A00.0Y-2A00.0Z Brain stem tissue 6.12E-01 -5.14E-01 -5.31E-01
Glioma 2A00.0Y-2A00.0Z White matter tissue 3.46E-02 8.22E-01 9.66E-01
Head and neck cancer 2D42 Head and neck tissue 2.64E-14 7.31E-01 7.46E-01
HIV-associated neurocognitive impairment 8A2Y-8A2Z White matter tissue 7.66E-01 -1.36E-01 -2.64E-01
Huntington's disease 8A01.10 Whole blood 3.54E-01 1.78E-01 3.18E-01
Idiopathic pulmonary fibrosis CB03.4 Lung tissue 1.96E-01 -2.41E-01 -2.02E-01
Immunodeficiency 4A00-4A20 Peripheral blood 7.07E-01 -3.08E-02 -1.48E-01
Influenza 1E30 Whole blood 2.88E-04 -2.19E+00 -1.03E+01
Interstitial cystitis GC00.3 Bladder tissue 1.39E-04 9.24E-01 4.77E+00
Intracranial aneurysm 8B01.0 Intracranial artery 8.12E-01 7.61E-01 4.24E-01
Irritable bowel syndrome DD91.0 Rectal colon tissue 3.28E-01 -1.04E-01 -2.42E-01
Ischemic stroke 8B11 Peripheral blood 1.28E-01 9.68E-02 2.44E-01
Juvenile idiopathic arthritis FA24 Peripheral blood 3.01E-11 -3.51E-01 -9.05E-01
Lateral sclerosis 8B60.4 Skin 1.42E-01 6.63E-01 1.04E+00
Lateral sclerosis 8B60.4 Cervical spinal cord 9.94E-01 -2.02E-01 -4.22E-01
Liver cancer 2C12.0 Liver tissue 6.19E-20 -1.17E+00 -2.33E+00
Liver failure DB99.7-DB99.8 Liver tissue 1.24E-03 -8.01E-01 -1.43E+00
Lung cancer 2C25 Lung tissue 9.41E-01 1.84E-01 2.07E-01
Lupus erythematosus 4A40 Whole blood 5.11E-04 2.51E-01 4.62E-01
Major depressive disorder 6A70-6A7Z Hippocampus 7.05E-01 -1.06E-01 -1.92E-01
Major depressive disorder 6A70-6A7Z Whole blood 8.04E-01 -3.79E-02 -1.19E-01
Melanoma 2C30 Skin 5.18E-01 2.20E-01 2.95E-01
Multiple myeloma 2A83.1 Peripheral blood 5.60E-01 -3.33E-01 -2.28E-01
Multiple myeloma 2A83.1 Bone marrow 1.57E-08 1.29E+00 6.20E+00
Multiple sclerosis 8A40 Plasmacytoid dendritic cells 2.95E-01 -2.43E-01 -4.45E-01
Myelodysplastic syndrome 2A36-2A3Z Bone marrow 3.76E-04 3.91E-01 6.81E-01
Myelofibrosis 2A20.2 Whole blood 6.63E-03 2.17E+00 8.28E+00
Myocardial infarction BA41-BA50 Peripheral blood 2.64E-03 -2.65E-01 -3.68E-01
Myopathy 8C70.6 Muscle tissue 4.02E-02 1.08E+00 1.41E+00
Neonatal sepsis KA60 Whole blood 2.18E-05 2.23E-01 4.33E-01
Neuroectodermal tumour 2A00.11 Brain stem tissue 2.71E-01 3.77E-01 6.82E-01
Non-alcoholic fatty liver disease DB92 Liver tissue 4.14E-01 7.09E-01 8.33E-01
Obesity related type 2 diabetes 5A11 Omental adipose tissue 2.11E-01 2.33E-01 1.88E-01
Olive pollen allergy CA08.00 Peripheral blood 3.33E-01 -2.34E-01 -7.30E-01
Oral cancer 2B6E Oral tissue 1.08E-03 6.45E-01 5.19E-01
Osteoarthritis FA00-FA0Z Synovial tissue 1.24E-01 9.65E-01 6.82E-01
Osteoporosis FB83.1 Bone marrow 1.32E-01 -1.17E+00 -1.39E+00
Ovarian cancer 2C73 Ovarian tissue 5.36E-04 2.39E+00 1.88E+00
Pancreatic cancer 2C10 Pancreas 4.54E-01 3.06E-01 3.17E-01
Parkinson's disease 8A00.0 Substantia nigra tissue 2.91E-01 1.10E+00 9.19E-01
Pediatric respiratory syncytial virus infection CA40.11 Peripheral blood 3.65E-05 4.66E-01 1.80E+00
Pituitary cancer 2D12 Pituitary tissue 6.88E-01 -3.32E-01 -5.79E-01
Pituitary gonadotrope tumour 2D12 Pituitary tissue 4.53E-03 -6.69E-01 -1.03E+00
Polycystic ovary syndrome 5A80.1 Vastus lateralis muscle 6.91E-01 6.19E-02 2.45E-01
Polycythemia vera 2A20.4 Whole blood 5.80E-05 1.95E-01 7.30E-01
Pompe disease 5C51.3 Biceps muscle 8.50E-01 9.34E-02 1.92E-01
Preterm birth KA21.4Z Myometrium 2.55E-01 -1.41E+00 -8.48E-01
Prostate cancer 2C82 Prostate 9.46E-01 -1.22E-01 -1.37E-01
Psoriasis EA90 Skin 3.50E-25 1.43E+00 2.13E+00
Rectal cancer 2B92 Rectal colon tissue 6.91E-04 4.64E-01 2.48E+00
Renal cancer 2C90-2C91 Kidney 6.90E-04 -1.00E+00 -1.38E+00
Retinoblastoma 2D02.2 Uvea 6.28E-07 -1.47E+00 -4.24E+00
Rheumatoid arthritis FA20 Synovial tissue 3.67E-04 1.95E+00 2.55E+00
Rhinovirus infection CA42.1 Nasal epithelium tissue 8.06E-02 1.64E-01 4.40E-01
Schizophrenia 6A20 Prefrontal cortex 3.27E-02 2.76E-01 2.05E-01
Schizophrenia 6A20 Superior temporal cortex 1.21E-01 1.74E-01 3.90E-01
Scleroderma 4A42.Z Whole blood 3.65E-03 -2.51E-01 -1.17E+00
Seizure 8A60-8A6Z Whole blood 6.84E-01 1.01E-01 2.83E-01
Sensitive skin EK0Z Skin 1.06E-01 3.06E-01 2.27E+00
Sepsis with septic shock 1G41 Whole blood 3.34E-19 3.19E-01 7.18E-01
Shwachman-Diamond syndrome 3A70.0 Bone marrow 4.42E-03 5.86E-01 1.71E+00
Sickle cell disease 3A51.0-3A51.3 Peripheral blood 1.07E-01 3.86E-01 5.17E-01
Simpson golabi behmel syndrome LD2C Adipose tissue 6.02E-01 1.90E-01 3.82E-01
Sjogren's syndrome 4A43.2 Salivary gland tissue 5.83E-01 2.47E-03 1.83E-02
Skin cancer 2C30-2C3Z Skin 3.88E-10 4.84E-01 7.58E-01
Thrombocythemia 3B63 Whole blood 1.39E-02 1.77E-01 6.79E-01
Thrombocytopenia 3B64 Whole blood 4.81E-01 2.67E-02 7.88E-02
Thyroid cancer 2D10 Thyroid 1.63E-35 1.30E+00 2.07E+00
Tibial muscular dystrophy 8C75 Muscle tissue 3.97E-06 7.24E-01 1.97E+00
Tuberous sclerosis complex LD2D.2 Perituberal tissue 9.50E-02 3.22E-01 6.63E-01
Type 2 diabetes 5A11 Liver tissue 8.44E-01 2.04E-01 9.28E-01
Ureter cancer 2C92 Urothelium 5.08E-01 -4.55E-02 -1.72E-01
Uterine cancer 2C78 Endometrium tissue 7.30E-09 8.22E-01 7.94E-01
Vitiligo ED63.0 Skin 4.68E-01 1.90E-01 4.88E-01
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⏷ Show the Full List of DME Expression Under 107 Diseases

The Drug Therapeutic Target (DTT) Role of This DME

DME DTT Name Purine nucleoside phosphorylase (PNP) DTT Info
DME DTT Type Clinical trial
5 Clinical Trial Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
2'3'-Dideoxyinosine DMZWNQF N. A. N. A. Phase 2 [1]
BCX-3408 DMRSG31 Autoimmune diabetes 5A10 Phase 2 [2]
Forodesine DME2W4T B-cell acute lymphoblastic leukaemia 2B33.3 Phase 1/2 [3]
Guanosine DM4T5LH N. A. N. A. Phase 1 [1]
Peldesine DMHV58T N. A. N. A. Phase 1 [1]
1 Discontinued Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
CI-972 DM9ZBO0 Rheumatoid arthritis FA20 Discontinued in Phase 1 [4]
27 Investigative Drug(s) Targeting This DTT
Drug Name Drug ID Indication ICD 11 Highest Status REF
(+/-)-5'-deoxy-4'-fluoro-5'-methylthio-DADMe-ImmH DMQP5U9 Discovery agent N.A. Investigative [5]
2-Hydroxymethyl-Pyrrolidine-3,4-Diol DM7MUZ1 Discovery agent N.A. Investigative [6]
3-((2-Pyrrolidine-1-yl)-ethyl)uracil DMSGX7V Discovery agent N.A. Investigative [7]
3-Deoxyguanosine DMFQUGE Discovery agent N.A. Investigative [1]
5'-deoxy-4'-hydroxy-5'-methylthio-DADMe-ImmH DMRFH9U Discovery agent N.A. Investigative [5]
5'-Methylthio-ImmH DM3LY0Q Discovery agent N.A. Investigative [5]
5'-methylthio-immucillin-H DMK52UH Discovery agent N.A. Investigative [7]
5'-phenylthio-ImmH DMQMZ0Y Discovery agent N.A. Investigative [5]
7-tert-butyl-2, 3-dihydro-3, 3-dimethyl substituted dihydrofuran 30 (DHDMBF30) DMSU06X Discovery agent N.A. Investigative [8]
8-amino-9-benzylguanine DMSNG7M N. A. N. A. Investigative [8]
8-AMINOGUANINE DMYXJG7 Discovery agent N.A. Investigative [9]
8-aminoguanosine DM0JEA6 Discovery agent N.A. Investigative [10]
8-aza-DADMe-ImmH DMBVFKR Discovery agent N.A. Investigative [11]
8-Azaguanine DM7VP90 Discovery agent N.A. Investigative [1]
8-Iodo-Guanine DM3K1EO Discovery agent N.A. Investigative [1]
9-(5,5-Difluoro-5-Phosphonopentyl)Guanine DMGFQLE Discovery agent N.A. Investigative [1]
9-Deazahypoxanthine DM3G6LY Discovery agent N.A. Investigative [1]
9-Deazainosine DME7ONQ Discovery agent N.A. Investigative [1]
9-DEAZAINOSINE-2',3'-O-ETHYLIDENEPHOSPHONATE DM9BCDT Discovery agent N.A. Investigative [12]
Aza-C-nucleosides DMOSI4U Discovery agent N.A. Investigative [13]
DADMe-ImmG DMJIFY3 Discovery agent N.A. Investigative [11]
GUANOSINE-2',3'-O-ETHYLIDENEPHOSPHONATE DMCN56S Discovery agent N.A. Investigative [12]
GUANOSINE-2',3'-O-METHYLIDENEPHOSPHONATE DMRITFU Discovery agent N.A. Investigative [12]
Hypoxanthine DMLSABI Discovery agent N.A. Investigative [1]
Immucillin-G DMX2NKO Discovery agent N.A. Investigative [13]
MT-Immucillin-H DMK2FOX Discovery agent N.A. Investigative [14]
Ribose-1-Phosphate DM7V8DZ Discovery agent N.A. Investigative [1]
⏷ Show the Full List of 27 Investigative Drug(s)

References

1 How many drug targets are there Nat Rev Drug Discov. 2006 Dec;5(12):993-6.
2 BCX-4208 (RO5092888), a Purine Nucleoside Phosphorylase (PNP) Inhibitor, Is a Novel, Potent Orally Active Anti-T-Cell and B-Cell Agent. 50th ASH Annual Meeting and Exposition. 2008.
3 Forodesine has high antitumor activity in chronic lymphocytic leukemia and activates p53-independent mitochondrial apoptosis by induction of p73 an... Blood. 2009 Aug 20;114(8):1563-75.
4 Inhibitors of human purine nucleoside phosphorylase. Synthesis of pyrrolo[3,2-d]pyrimidines, a new class of purine nucleoside phosphorylase inhibitors as potentially T-cell selective immunosuppressive agents. Description of 2,6-diamino-3,5-dihydro-7-(3-thienylmethyl)-4H-pyrrolo[3,2-d] pyrimidin-4-one. J Med Chem. 1992 May 1;35(9):1605-9.
5 Immucillins in custom catalytic-site cavities. Bioorg Med Chem Lett. 2008 Nov 15;18(22):5900-3.
6 DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Nucleic Acids Res. 2011 Jan;39(Database issue):D1035-41.
7 Exploring new inhibitors of Plasmodium falciparum purine nucleoside phosphorylase. Eur J Med Chem. 2010 Nov;45(11):5140-9.
8 Expression of human malaria parasite purine nucleoside phosphorylase in host enzyme-deficient erythrocyte culture. Enzyme characterization and identification of novel inhibitors. J Biol Chem. 1986 Sep 5;261(25):11667-73.
9 Nucleosides. 5. Synthesis of guanine and formycin B derivatives as potential inhibitors of purine nucleoside phosphorylase. J Med Chem. 1993 Apr 16;36(8):1024-31.
10 Differential metabolism of guanine nucleosides by human lymphoid cell lines. Proc Soc Exp Biol Med. 1985 Sep;179(4):427-31.
11 Achieving the ultimate physiological goal in transition state analogue inhibitors for purine nucleoside phosphorylase. J Biol Chem. 2003 Aug 22;278(34):31465-8.
12 The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42.
13 Exploring structure-activity relationships of transition state analogues of human purine nucleoside phosphorylase. J Med Chem. 2003 Jul 17;46(15):3412-23.
14 Plasmodium falciparum purine nucleoside phosphorylase: crystal structures, immucillin inhibitors, and dual catalytic function. J Biol Chem. 2004 Apr 30;279(18):18103-6.
15 Functional analysis of purine nucleoside phosphorylase as a key enzyme in ribavirin metabolism. Drug Metab Pharmacokinet. 2014;29(2):211-4.