Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20226 (TATA-binding protein)
 1,297 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The TATA-box binding protein (TBP) is required by eukaryotic RNA polymerases to bind to the TATA box, an eight-basepair DNA promoter element, to initiate transcription. Carcinogen adducts that bind to the TATA box can hamper this important process. Benzo[a]pyrene (BP) is a representative chemical carcinogen that can be metabolically converted to highly reactive benzo[a]pyrene diol epoxides (BPDE), which in turn can form chemically stereoisomeric BP-DNA adducts. Depending on the TATA-bound adduct's location and stereochemistry, TATA/TBP binding can be decreased or increased. Our previous study interpreted the location-dependent effect in terms of conformational freedom and major-groove space available to BP. Here we further explore specific structural changes of the TATA/TBP complex to help interpret the stereochemical effect in terms of the flexibility of the TATA bases that frame the intercalated adduct. Thermodynamic analyses using molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) yield large standard deviations, which make the computed binding free energies the same within the error bars and point to current limitations of free energy calculations of large and highly charged systems like DNA/protein complexes.
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PMID:Stereochemistry and position-dependent effects of carcinogens on TATA/TBP binding. 1638 64