Thymidylate kinase

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thymidylate kinase
1e2d.jpg
Thymidylate kinase dimer, Human
Identifiers
EC number 2.7.4.9
Databases
IntEnz IntEnz view
BRENDA BRENDA entry
ExPASy NiceZyme view
KEGG KEGG entry
MetaCyc metabolic pathway
PRIAM profile
PDB structures RCSB PDB PDBe PDBsum
Gene Ontology AmiGO / QuickGO
Thymidylate kinase
Identifiers
SymbolThymidylate_kin
Pfam PF02223
InterPro IPR000062
PROSITE PDOC01034

Thymidylate kinase (EC 2.7.4.9; dTMP kinase) catalyzes the phosphorylation of thymidine 5'-monophosphate (dTMP) to form thymidine 5'-diphosphate (dTDP) in the presence of ATP and magnesium:

Contents

ATP + thymidine 5'-phosphate ADP + thymidine 5'-diphosphate

Thymidylate kinase is a ubiquitous enzyme of about 25 Kd and is important in the dTTP synthesis pathway for DNA synthesis. The function of dTMP kinase in eukaryotes comes from the study of a cell cycle mutant, cdc8, in Saccharomyces cerevisiae . Structural and functional analyses suggest that the cDNA codes for authentic human dTMP kinase. The mRNA levels and enzyme activities corresponded to cell cycle progression and cell growth stages. [1]

Thymidylate kinase's subfamily is predicted thymidylate kinase, TKRP1. InterPro :  IPR014505

Human protein DTYMK contains this domain.

Structural studies

As of late 2007, 40 structures have been solved for this class of enzymes, with PDB accession codes 1E2D, 1E2E, 1E2F, 1E2G, 1E2Q, 1E98, 1E99, 1E9A, 1E9B, 1E9C, 1E9D, 1E9E, 1E9F, 1G3U, 1GSI, 1GTV, 1MRN, 1MRS, 1N5I, 1N5J, 1N5K, 1N5L, 1NMX, 1NMY, 1NMZ, 1NN0, 1NN1, 1NN3, 1NN5, 1TMK, 1W2G, 1W2H, 2CCG, 2CCJ, 2CCK, 2PBR, 2TMK, 3TMK, 4TMK, and 5TMP.

See also

Related Research Articles

Kinase Enzyme catalyzing transfer of phosphate groups onto specific substrates

In biochemistry, a kinase is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the substrate gains a phosphate group and the high-energy ATP molecule donates a phosphate group. This transesterification produces a phosphorylated substrate and ADP. Conversely, it is referred to as dephosphorylation when the phosphorylated substrate donates a phosphate group and ADP gains a phosphate group. These two processes, phosphorylation and dephosphorylation, occur four times during glycolysis.

A salvage pathway is a pathway in which a biological product is produced from intermediates in the degradative pathway of its own or a similar substance. The term often refers to nucleotide salvage in particular, in which nucleotides are synthesized from intermediates in their degradative pathway.

Thymidine kinase InterPro Family

Thymidine kinase is an enzyme, a phosphotransferase : 2'-deoxythymidine kinase, ATP-thymidine 5'-phosphotransferase, EC 2.7.1.21. It can be found in most living cells. It is present in two forms in mammalian cells, TK1 and TK2. Certain viruses also have genetic information for expression of viral thymidine kinases. Thymidine kinase catalyzes the reaction:

Nucleoside-diphosphate kinase class of enzymes

Nucleoside-diphosphate kinases are enzymes that catalyze the exchange of terminal phosphate between different nucleoside diphosphates (NDP) and triphosphates (NTP) in a reversible manner to produce nucleotide triphosphates. Many NDP serve as acceptor while NTP are donors of phosphate group. The general reaction via ping-pong mechanism is as follows: XDP + YTP ←→ XTP + YDP. NDPK activities maintain an equilibrium between the concentrations of different nucleoside triphosphates such as, for example, when guanosine triphosphate (GTP) produced in the citric acid (Krebs) cycle is converted to adenosine triphosphate (ATP). Other activities include cell proliferation, differentiation and development, signal transduction, G protein-coupled receptor, endocytosis, and gene expression.

HAT medium used in microbiology and immunology

HAT Medium is a selection medium for mammalian cell culture, which relies on the combination of aminopterin, a drug that acts as a powerful folate metabolism inhibitor by inhibiting dihydrofolate reductase, with hypoxanthine and thymidine which are intermediates in DNA synthesis. The trick is that aminopterin blocks DNA de novo synthesis, which is absolutely required for cell division to proceed, but hypoxanthine and thymidine provide cells with the raw material to evade the blockage, provided that they have the right enzymes, which means having functioning copies of the genes that encode them.

Purine nucleoside phosphorylase InterPro Family

Purine nucleoside phosphorylase (PNP) also known as PNPase and inosine phosphorylase is an enzyme that in humans is encoded by the NP gene.

Nucleic acid metabolism

Nucleic acid metabolism is the process by which nucleic acids are synthesized and degraded. Nucleic acids are polymers of nucleotides. Nucleotide synthesis is an anabolic mechanism generally involving the chemical reaction of phosphate, pentose sugar, and a nitrogenous base. Destruction of nucleic acid is a catabolic reaction. Additionally, parts of the nucleotides or nucleobases can be salvaged to recreate new nucleotides. Both synthesis and degradation reactions require enzymes to facilitate the event. Defects or deficiencies in these enzymes can lead to a variety of diseases.

Serine/threonine-specific protein kinase group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins

A serine/threonine protein kinase is a kinase enzyme that phosphorylates the OH group of serine or threonine. At least 125 of the 500+ human protein kinases are serine/threonine kinases (STK).

Thymidylate synthase mammalian protein found in Homo sapiens

Thymidylate synthase (TS) is an enzyme that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP). Thymidine is one of the nucleotides in DNA. With inhibition of TS, an imbalance of deoxynucleotides and increased levels of dUMP arise. Both cause DNA damage.

GMP synthase mammalian protein found in Homo sapiens

Guanosine monophosphate synthetase, also known as GMPS is an enzyme that converts xanthosine monophosphate to guanosine monophosphate.

Inosine monophosphate synthase mammalian protein found in Homo sapiens

Bifunctional purine biosynthesis protein PURH is a protein that in humans is encoded by the ATIC gene.

Thymidine kinase 1 protein-coding gene in the species Homo sapiens

Thymidine kinase 1, soluble, is a human thymidine kinase.

dUTP diphosphatase InterPro Family

In enzymology, a dUTP diphosphatase (EC 3.6.1.23) is an enzyme that catalyzes the chemical reaction

In enzymology, a thiamine-phosphate diphosphorylase is an enzyme that catalyzes the chemical reaction

In enzymology, a (deoxy)nucleoside-phosphate kinase is an enzyme that catalyzes the chemical reaction

Guanylate kinase InterPro Family

In enzymology, a guanylate kinase is an enzyme that catalyzes the chemical reaction

In enzymology, a nucleoside-triphosphate-adenylate kinase is an enzyme that catalyzes the chemical reaction

DTYMK protein-coding gene in the species Homo sapiens

Thymidylate kinase also known as deoxythymidylate kinase or dTMP kinase is an enzyme that in humans is encoded by the DTYMK gene. and belongs to thymidylate kinase family of proteins.

Trifluridine/tipiracil chemical compound

Trifluridine/tipiracil is a combination drug that is used as a third- or fourth-line treatment of metastatic colorectal cancer, after chemotherapy and targeted therapeutics have failed. It is a combination of two active pharmaceutical ingredients: trifluridine, a nucleoside analog, and tipiracil, a thymidine phosphorylase inhibitor. Tipiracil prevents rapid metabolism of trifluridine, increasing the bioavailability of trifluridine.

Thymidine kinase is an enzyme, a phosphotransferase : 2'-deoxythymidine kinase, ATP-thymidine 5'-phosphotransferase, EC 2.7.1.21 that catalyzes the reaction:

References

  1. Li C, Huang SH, Tang A, Drisco B, Zhang SQ, Seeger R, Jong A (1994). "Human dTMP kinase: gene expression and enzymatic activity coinciding with cell cycle progression and cell growth". DNA Cell Biol. 13 (5): 461–471. doi:10.1089/dna.1994.13.461. PMID   8024690.
This article incorporates text from the public domain Pfam and InterPro: IPR000062