Details of Drug-Metabolizing Enzyme (DME)

General Information of DME (ID: DMEN006)
DME Name Nucleoside diphosphate kinase (NME4), Homo sapiens
Gene Name NME4
UniProt ID
NDKM_HUMAN
EC Number    EC: 2.7.4.10     (Click to Show/Hide the Complete EC Tree)
Transferase
Kinase
Phosphotransferase
EC: 2.7.4.10
Lineage    Species: Homo sapiens     (Click to Show/Hide the Complete Species Lineage)
Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens
      Click to Show/Hide the Molecular/Functional Data (Sequence/Structure/Pathway/Function) of This DME
Sequence
MGGLFWRSALRGLRCGPRAPGPSLLVRHGSGGPSWTRERTLVAVKPDGVQRRLVGDVIQR
FERRGFTLVGMKMLQAPESVLAEHYQDLRRKPFYPALIRYMSSGPVVAMVWEGYNVVRAS
RAMIGHTDSAEAAPGTIRGDFSVHISRNVIHASDSVEGAQREIQLWFQSSELVSWADGGQ
HSSIHPA
Structure
1EHW ;
Function Major role in the synthesis of nucleoside triphosphates other than ATP. The ATP gamma phosphate is transferred to the NDP beta phosphate via a ping-pong mechanism, using a phosphorylated active-site intermediate. Through the catalyzed exchange of gamma-phosphate between di- and triphosphonucleosides participates in regulation of intracellular nucleotide homeostasis. Binds to anionic phospholipids, predominantly to cardiolipin; the binding inhibits its phosphotransfer activity. Acts as mitochondria-specific NDK; its association with cardiolipin-containing mitochondrial inner membrane is coupled to respiration suggesting that ADP locally regenerated in the mitochondrion innermembrane space by its activity is directly taken up via ANT ADP/ATP translocase into the matrix space to stimulate respiratory ATP regeneration. Proposed to increase GTP-loading on dynamin-related GTPase OPA1 in mitochondria. In vitro can induce liposome cross-linking suggesting that it can cross-link inner and outer membranes to form contact sites, and promotes intermembrane migration of anionic phosphoplipids. Promotes the redistribution of cardiolipin between the mitochondrial inner membrane and outer membrane which is implicated in pro-apoptotic signaling.
Full List of Drug(s) Metabolized by This DME
      Drugs Approved by FDA Click to Show/Hide the Full List of Drugs:          1 Drugs
Lamivudine
 Drug Info Approved Human immunodeficiency virus infection ICD11: 1C60 [1]
      Drugs in Phase 4 Clinical Trial Click to Show/Hide the Full List of Drugs:          1 Drugs
Tenofovir disoproxil
 Drug Info Phase 4 Human immunodeficiency virus infection ICD11: 1C60 [2]
      Drugs in Phase 2 Clinical Trial Click to Show/Hide the Full List of Drugs:          1 Drugs
Amdoxovir
 Drug Info Phase 2 Hepatitis B virus infection ICD11: 1E50-1E51 [3]
      Discontinued/withdrawn Drugs Click to Show/Hide the Full List of Drugs:          1 Drugs
R7128
 Drug Info Discontinued in Phase 2 Hepatitis C virus infection ICD11: 1E50-1E51 [4]
Full List of Metabolic Reactions (MR) Catalyzed by This DME
MR ID Reactant Product MR Type Source Drug REF
MR008549 DXG-DP DXG-triphosphate (DXG-TP) Conjugation - Phosphorylation Amdoxovir [3]
MR009895 5-Aza2' deoxycytidine diphosphate 5-Aza2' -dexycytidine triphosphate Unclear - Unclear Azacitidine [5]
MR001405 Lamivudine diphosphate Lamivudine triphosphate Other reaction - Phosphorylation lamivudine [6], [7]
MR009413 PSI-6130-DP PSI-6130-TP Unclear - Unclear R7128 [4]
MR013668 GS-331007-MP GS-331007-TP Unclear - Unclear Sofosbuvir [8]
MR006161 Tenofovir Monophosphate Tenofovir Diphosphate Conjugation - Phosphorylation Tenofovir disoproxil [2]
⏷ Show the Full List of 6 MR(s)
References
1 Model for intracellular Lamivudine metabolism in peripheral blood mononuclear cells ex vivo and in human immunodeficiency virus type 1-infected adolescents Antimicrob Agents Chemother. 2006 Aug;50(8):2686-94. doi: 10.1128/AAC.01637-05.
2 Tenofovir disoproxil fumarate: clinical pharmacology and pharmacokinetics
3 Anabolism of amdoxovir: phosphorylation of dioxolane guanosine and its 5'-phosphates by mammalian phosphotransferases
4 Characterization of the metabolic activation of hepatitis C virus nucleoside inhibitor beta-D-2'-Deoxy-2'-fluoro-2'-C-methylcytidine (PSI-6130) and identification of a novel active 5'-triphosphate species
5 5-Azacytidine/Azacitidine
6 Model for intracellular Lamivudine metabolism in peripheral blood mononuclear cells ex vivo and in human immunodeficiency virus type 1-infected adolescents. Antimicrob Agents Chemother. 2006 Aug;50(8):2686-94.
7 Antiviral and cellular metabolism interactions between Dexelvucitabine and lamivudine Antimicrob Agents Chemother. 2007 Jun;51(6):2130-5. doi: 10.1128/AAC.01543-06.
8 Species differences in liver accumulation and metabolism of nucleotide prodrug sofosbuvir

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