4Q78

Structure-assisted design of carborane-based inhibitors of carbonic anhydrase

Summary for 4Q78

• Entry DOI: 10.2210/pdb4q78/pdb
• Related: 4MDG
• Descriptor: Carbonic anhydrase 2, ZINC ION, 1-(sulfamoylamino)methyl-1,2-dicarba-closo-dodecaborane, ... (5 entities in total)
• Functional Keywords: carbonic anhydrase, lyase-lyase inhibitor complex, lyase/lyase inhibitor
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P00918
• Total number of polymer chains: 1
• Total formula weight: 30020.86

Authors

Mader, P.,Brynda, J.,Rezacova, P. (deposition date: 2014-04-24, release date: 2015-03-18, Last modification date: 2024-02-28)

Primary citation

Mader, P.,Pecina, A.,Cigler, P.,Lepsik, M.,Sicha, V.,Hobza, P.,Gruner, B.,Fanfrlik, J.,Brynda, J.,Rezacova, P.
Carborane-based carbonic anhydrase inhibitors: insight into CAII/CAIX specificity from a high-resolution crystal structure, modeling, and quantum chemical calculations.
Biomed Res Int, 2014:389869-389869, 2014

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.

PubMed: 25309911
DOI: 10.1155/2014/389869

Experimental method

X-RAY DIFFRACTION (1 Å)