Wang, Jenna L. and Guo, Jian-Xin and Zhang, Qi-Yuan and Wu, Jay J.-Q. and Seifert, Roland and Lushington, Gerald H.
A conformational transition in the adenylyl cyclase catalytic site yields different binding modes for ribosyl-modified
and unmodified nucleotide inhibitors. Bioorganic & Medicinal Chemistry 15 (8), pp. 2993-3002.
Abstract—Adenylyl cyclases (ACs) are promising pharmacological targets for treating heart failure, cancer, and psychosis. Ribosesubstituted nucleotides have been reported as a potent family of AC inhibitors. In silico analysis of the docked conformers of such
nucleotides in AC permits assembly of a consistent, intuitive QSAR model with strong correlation relative to measured pKi values. Energy decomposition suggests that the MANT group effects an AC conformational transition upon ligand binding.
|Institutions:||Chemistry and Pharmacy > Institute of Pharmacy > Pharmacology and Toxicology (Prof. Schlossmann formerly Prof. Seifert)|
|Subjects:||500 Science > 570 Life sciences|
600 Technology > 610 Medical sciences Medicine
|Refereed:||Yes, this version has been refereed|
|Created at the University of Regensburg:||Unknown|
|Deposited On:||28 Jan 2008 15:11|
|Last Modified:||20 Jul 2011 21:11|