Document Detail


The effect of the nitrosourea analog of thymidine, 3'-[3-(2-chloroethyl)-3-nitrosoureido]-3'-deoxythymidine, on Escherichia coli thymidine kinase.
MedLine Citation:
PMID:  7002216     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Escherichia coli thymidine kinase (ATP:thymidine 5'-phosphotransferase, EC 2.7.1.21) is irreversibly inactivated by incubation with 3'-[3-(2-chloroethyl)-3-nitrosoureido]-3'-deoxythymidine (3'-CTNU). The inactivation of the enzyme followed first-order kinetics even after loss of 96% of the original activity. This indicates that the inactivation process is a one-kill phenomenon and not a generation of less active enzyme. The addition of a preincubated aqueous solution of 3'-CTNU to the enzyme reaction mixture did not inactivate the enzyme. ATP . Mg2+ but not thymidine protects the enzyme from inactivation by 3'-CTNU. The allosteric regulators, dTTP, dCTP and dCDP also afforded complete protection of the enzyme from inactivation by 3'-CTNU. These data indicate that the dimer form of the enzyme is completely resistant to inactivation by 3'-CTNU, but the monomer form of the enzyme is sensitive. The specificity of the protection is supported by the finding that neither ATP . Mg2+ nor thymidine protect yeast alcohol dehydrogenase from inactivation by this nitrosourea analog of thymidine.
Authors:
M S Chen; T S Lin; W H Prusoff
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  616     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  1980 Nov 
Date Detail:
Created Date:  1981-02-26     Completed Date:  1981-02-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  35-40     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / pharmacology
Allosteric Regulation
Antineoplastic Agents / pharmacology*
Dideoxynucleosides*
Escherichia coli / enzymology*
Magnesium / pharmacology
Nitrosourea Compounds / pharmacology*
Thymidine / analogs & derivatives*,  pharmacology
Thymidine Kinase / antagonists & inhibitors*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Dideoxynucleosides; 0/Nitrosourea Compounds; 50-89-5/Thymidine; 56-65-5/Adenosine Triphosphate; 65174-26-7/3'-(3-(2-chloroethyl)-3-nitrosourea)-3'-deoxythymidine; 7439-95-4/Magnesium; EC 2.7.1.21/Thymidine Kinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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