Wyniki wyszukiwania

1

Modulation of human deoxycytidine kinase activity as a response to cellular stress induced by NaF

100%

Csapo Z., Sasvari-Szekely M., Spasokoukotskaja T., Staub M.

Acta Biochimica Polonica

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2001

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tom 48

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nr 1

Deoxycytidine kinase (dCK) is one of the key enzymes of deoxynucleoside salvage supplying resting lymphocytes with DNA precursors for synthesis and repair. The level of dCK activity is especially important in chemotherapy with the use of deoxynucleoside analogues like arabinosyl cytosine (Citarabid, ara-C), or 2-chloro-deoxyadenosine (Cladribine, CdA). Previous results showed that Cladribine treatment of human lymphocytes increased several fold the activity of dCK without increasing the amount of dCK protein itself (Sasvari-Székely, et al., 1998, Biochem. Pharmacol. 56, 1175), and a possible post-translational modification was suggested. This theory was further investigated using NaF as an inhibitor of protein phosphatases. It was shown that NaF treatment of cells elevated dCK activity while inhibiting DNA synthesis. The possible mechanism of dCK activa- tion/inactivation induced by exposure of cell cultures to different agents is discussed.

2

Structural aspects of the inhibition and catalytic mechanism of thymidylate synthase

84%

Hardy L. W.

Acta Biochimica Polonica

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1995

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tom 42

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nr 4

Thymidylate synthase (TS) is a target for anticancer drugs, due to its unique role in the biosynthesis of an essential DNA precursor. The X-ray structures available for several bacterial enzymes have been used to design novel inhibitors of TS, to structurally analyze the binding mode of existing inhibitors, and to propose catalytic roles for amino-acid residues on the protein. The first part of this paper describes some aspects of structure-based drug design, including a recent result from the groups of Montfort and Maley emphasizing the importance of conformational changes in inhibitor binding. The second part of the paper describes the work of the author on the TS mechanism, especially the catalytic roles of active site amino acids Asnl77 and Glu58 in TS from Escherichia coli. An important function for Glu58 is proposed to be preventing the excessive stabilization of a covalent intermediate. The use of isotope effects to probe the mechanistic basis for stimulation of E. coli TS by magnesium ions, and to identify differences between the E. coli and human enzymes, is described. The hypothesis that N5 of tetrahydrofolate provides the basicity for deprotonation of the nucleotide is also discussed.

3

Stucture-activity relationships for phosphorylation of nucleoside analogs to monophosphates by nucleoside kinases

84%

Johansson N. G., Eriksson S.

Acta Biochimica Polonica

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1996

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tom 43

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nr 1

The mammalian deoxyribonucleoside kinases thymidine kinase 1 and 2, deoxy- cytidine kinase and deoxyguanosine kinase phosphorylate deoxyribonucleosides and provide an alternative to de novo synthesis of DNA precursors. Their activities are essential for activation of several chemotherapeutically important nucleoside analogs. These four salvage kinase enzymes exhibit distinct substrate specificities for nucleoside analogs modified in the base and glycon moieties. In this review their, structure-activity relationships are discussed. Alternative routes for phosphorylation of nucleoside analogs are also reviewed, such as the phosphotransfer capacity of 5'-nucleotidase and protein kinases.

4

Modulation of human deoxycytidine kinase activity as a response to different cellular stresses

67%

Sasvari-Szekely M., Csapo Z., Spasokukockaja T., Talianidis I., Staub M.

Cellular and Molecular Biology Letters

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1999

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tom 04

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nr 3

5

Changes in murein composition during the cell cycle of Caulobacter crescentus

59%

Markiewicz Z., Bielecki J.

Acta Microbiologica Polonica

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1992

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tom 41

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nr 3-4

Ograniczanie wyników

3 Acta Biochimica Polonica

1 Acta Microbiologica Polonica

1 Cellular and Molecular Biology Letters

2 Csapo Z.

2 Sasvari-Szekely M.

2 Staub M.

1 Bielecki J.

1 Eriksson S.

1 Hardy L. W.

1 Johansson N. G.

1 Markiewicz Z.

1 Spasokoukotskaja T.

1 Spasokukockaja T.

1 Talianidis I.

1 2001

1 1999

1 1996

1 1995

1 1992

Modulation of human deoxycytidine kinase activity as a response to cellular stress induced by NaF

Structural aspects of the inhibition and catalytic mechanism of thymidylate synthase

Stucture-activity relationships for phosphorylation of nucleoside analogs to monophosphates by nucleoside kinases

Modulation of human deoxycytidine kinase activity as a response to different cellular stresses

Changes in murein composition during the cell cycle of Caulobacter crescentus