Inhibitors of Escherichia coli RNA polymerase specific for the single-stranded DNA of transcription intermediates. Tetrahedral cuprous chelates of 1,10-phenanthrolines.
Biochemistry
; 35(16): 5318-26, 1996 Apr 23.
Article
em En
| MEDLINE
| ID: mdl-8611519
ABSTRACT
Single-stranded DNA of the lacUV-5 promoter formed at the active site of Escherichia coli RNA polymerase during transcription is specifically cleaved by the redox active tetrahedral cuprous chelates of 1,10-phenanthroline and its derivatives. The cleavage sites are observed in the open, initiating, and elongating complexes. Redox-inert, tetrahedral cuprous chelates of neocuproine (2,9-dimethyl-1,10- phenanthroline) and its 5-phenyl and 4-phenyl derivatives protect the template strand of DNA from scission within these steady state intermediates and inhibit transcription. Although these cuprous chelates of neocuproine bind at multiple sites within three distinct enzyme intermediates, the highest affinity site is within the elongation complex. The I50 of 5 microM for the 21 5-phenylneocuproine cuprous complex ((5 phi NC)2Cu+) in runoff transcription therefore primarily reflects its intermediate. The neocuproine cuprous chelates are novel transcription inhibitors because they bind to single-stranded DNA sites generated during the course of catalysis by RNA polymerase.
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Coleções:
01-internacional
Contexto em Saúde:
3_ND
Base de dados:
MEDLINE
Assunto principal:
Compostos Organometálicos
/
Fenantrolinas
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Transcrição Gênica
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RNA Polimerases Dirigidas por DNA
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DNA Bacteriano
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DNA de Cadeia Simples
Idioma:
En
Revista:
Biochemistry
Ano de publicação:
1996
Tipo de documento:
Article