Download MendeleyCarborane-based carbonic anhydrase inhibitors: insight into CAII/CAIX specificity from a high-resolution crystal structure, modeling, and quantum chemical calculations.
Mader, P., Pecina, A., Cigler, P., Lepsik, M., Sicha, V., Hobza, P., Gruner, B., Fanfrlik, J., Brynda, J., Rezacova, P.(2014) Biomed Res Int 2014: 389869-389869
- PubMed: 25309911
- DOI: https://doi.org/10.1155/2014/389869
- Primary Citation of Related Structures:
4Q78 - PubMed Abstract:
Carborane-based compounds are promising lead structures for development of inhibitors of carbonic anhydrases (CAs). Here, we report structural and computational analysis applicable to structure-based design of carborane compounds with selectivity toward the cancer-specific CAIX isoenzyme. We determined the crystal structure of CAII in complex with 1-methylenesulfamide-1,2-dicarba-closo-dodecaborane at 1.0 Å resolution and used this structure to model the 1-methylenesulfamide-1,2-dicarba-closo-dodecaborane interactions with CAIX. A virtual glycine scan revealed the contributions of individual residues to the energy of binding of 1-methylenesulfamide-1,2-dicarba-closo-dodecaborane to CAII and CAIX, respectively.
Organizational Affiliation:
Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Vídeňská 1083, 140 00 Prague 4, Czech Republic ; Structural Genomics Consortium, University of Toronto, Toronto, ON, Canada M5G 1L7.
