About: Structure, physiological role, and specific inhibitors of human thymidine kinase 2 (TK2): Present and future

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Structure, physiological role, and specific inhibitors of human thymidine kinase 2 (TK2): Present and future
Creator	Balzarini, Jan Familiar, Olga Gago, Federico Herna´ndez, Ana-Isabel Negri, Ana Pe´rez-Pe´rez, Marı´a-Jesu´s Priego, Eva-Marı´a
Source	Medline; PMC
abstract	Human mitochondrial thymidine kinase (TK2) is a pyrimidine deoxynucleoside kinase (dNK) that catalyzes the phosphorylation of pyrimidine deoxynucleosides to their corresponding deoxynucleoside 5′‐monophosphates by γ‐phosphoryl transfer from ATP. In resting cells, TK2 is suggested to play a key role in the mitochondrial salvage pathway to provide pyrimidine nucleotides for mitochondrial DNA (mtDNA) synthesis and maintenance. However, recently the physiological role of TK2turned out to have direct clinical relevance as well. Point mutations in the gene encoding TK2 have been correlated to mtDNA disorders in a heterogeneous group of patients suffering from the so‐called mtDNA depletion syndrome (MDS). TK2 activity could also be involved in mitochondrial toxicity associated to prolonged treatment with antiviral nucleoside analogues like AZT and FIAU. Therefore, TK2 inhibitors can be considered as valuable tools to unravel the role of TK2 in the maintenance and homeostasis of mitochondrial nucleotide pools and mtDNA, and to clarify the contribution of TK2 activity to mitochondrial toxicity of certain antivirals. Highly selective TK‐2 inhibitors having an acyclic nucleoside structure and efficiently discriminating between TK‐2 and the closely related TK‐1 have already been reported. It is actually unclear whether these agents efficiently reach the inner mitochondrial compartment. In the present review article,structural features of TK2, MDS‐related mutations observed in TK2 and their role in MDS will be discussed. Also, an update on novel and selective TK2 inhibitors will be provided. © 2008 Wiley Periodicals, Inc. Med Res Rev, 28, No. 5, 797–820, 2008
has issue date	2008-05-05(xsd:dateTime)
bibo:doi	10.1002/med.20124
bibo:pmid	18459168
has license	no-cc
sha1sum (hex)	24f97a30b162379cb388e7304b05b9ef77f4bf02
schema:url	https://doi.org/10.1002/med.20124
resource representing a document's title	Structure, physiological role, and specific inhibitors of human thymidine kinase 2 (TK2): Present and future
has PubMed Central identifier	PMC7168489
has PubMed identifier	18459168
schema:publication	Med Res Rev
resource representing a document's body	covid:24f97a30b162379cb388e7304b05b9ef77f4bf02#body_text
is schema:about of	named entity 'salvage pathway' named entity 'antivirals' named entity 'selective' named entity 'TK2' named entity 'deoxynucleosides' named entity 'unravel' named entity 'Thymidine' named entity 'Inhibitors' named entity 'GENE' named entity 'transfer' named entity 'catalyzes' named entity 'activity' named entity 'structural' named entity 'reach' named entity 'features' named entity 'Therefore' named entity 'TK2' named entity 'inhibitors' named entity 'mtDNA' named entity 'homeostasis' named entity 'nucleoside' named entity 'AZT' named entity 'phosphoryl' named entity 'deoxynucleoside kinase' named entity 'mtDNA' named entity 'TK2' named entity 'physiological' named entity 'TK2' named entity 'mitochondrial' named entity 'TK-2' named entity 'mtDNA' named entity 'mitochondrial DNA' named entity 'salvage pathway' named entity 'mtDNA' named entity 'TK-2' named entity 'Human' named entity 'substrate specificity' named entity 'metabolism' named entity 'deoxyuridine' named entity 'TK1' named entity 'nucleoside' named entity 'enzyme' named entity 'heteroaromatic' named entity 'nucleosides' named entity 'dTTP' named entity 'TK2' named entity 'AZT' named entity 'inhibitory activity' named entity 'AZT' named entity 'TK2' named entity 'deoxycytidine' named entity 'conformational freedom' named entity 'carboxamide' named entity 'cytosol' named entity 'SDH' named entity 'substrate' named entity 'TK2' named entity 'binding site' named entity 'nucleoside' named entity 'dTTP' named entity 'TK1' named entity 'substrates' named entity 'mutation' named entity 'dCK' named entity 'AZT' named entity 'amino acid' named entity 'TK1' named entity 'radiolabeled' named entity 'TK2' named entity 'nucleosides' named entity 'TK2' named entity 'deprotonation' named entity 'substrates' named entity 'TK1' named entity 'hydrolyzed'

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