Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.1.108 (TAT)
 2,389 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An unusually slow association process which accounts for the bulk of its dichroic changes at 293 nm is observed for d(CAT-GGCC-ATG) when it reacts with actinomycin D (ACTD). This is in contrast to an order of magnitude faster association rates exhibited by oligomers containing a self-complementary tetranucleotide ACTD binding sequence (-TGCA-, -AGCT-, or -CGCG-). The number of drug molecules bound and the melting temperature increase upon ACTD binding are significantly higher for d(CAT-GGCC-ATG) than for other decamers studied. Temperature-dependent spectral measurements of this oligomer in the presence of ACTD suggest additional drug binding prior to denaturation. This particular decamer sequence may be unique, as other decamers containing central -GGCC- sequence and even those differing only by the terminal bases such as d(TAT-GGCC-ATA) and d(GAT-GGCC-ATC) are only weakly binding and do not exhibit such anomalously slow ACTD association kinetics, whereas the dodecamer d(CCAT-GGCC-ATGG) does. CD evidence indicates that, in contrast to the other -GGCC- containing oligomers, both d(CCAT-GGCC-ATGG) and its parent decamer exhibit nonstandard B conformations. The observed slow association kinetics and its interesting D/P dependence are rationalized in terms of a model in which the ACTD molecules initially end-stack and distort the oligomer duplex to a favorable ACTD-binding conformation so that intercalation at the central G-C sequence can occur via DNA breathing.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Observation of an anomalously slow association kinetics in the binding of actinomycin D to d(CATGGCCATG). 227 27