6YZT

Closo-carborane propyl-sulfonamide in complex with CA II

Summary for 6YZT

• Entry DOI: 10.2210/pdb6yzt/pdb
• Descriptor: Carbonic anhydrase 2, ZINC ION, Carborane propyl-sulfonamide, ... (4 entities in total)
• Functional Keywords: carbonic anhydrase, ca inhibitor, lyase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 29608.77

Authors

Kugler, M.,Brynda, J.,Pospisilova, K.,Rezacova, P. (deposition date: 2020-05-07, release date: 2020-10-28, Last modification date: 2024-01-24)

Primary citation

Kugler, M.,Holub, J.,Brynda, J.,Pospisilova, K.,Anwar, S.E.,Bavol, D.,Havranek, M.,Kral, V.,Fabry, M.,Gruner, B.,Rezacova, P.
The structural basis for the selectivity of sulfonamido dicarbaboranes toward cancer-associated carbonic anhydrase IX.
J Enzyme Inhib Med Chem, 35:1800-1810, 2020

PubMed Abstract: Human carbonic anhydrase IX (CA IX), a protein specifically expressed on the surface of solid tumour cells, represents a validated target both for anticancer therapy and diagnostics. We recently identified sulfonamide dicarbaboranes as promising inhibitors of CA IX with favourable activities both and . To explain their selectivity and potency, we performed detailed X-ray structural analysis of their interactions within the active sites of CA IX and CA II. Series of compounds bearing various aliphatic linkers between the dicarbaborane cluster and sulfonamide group were examined. Preferential binding towards the hydrophobic part of the active site cavity was observed. Selectivity towards CA IX lies in the shape complementarity of the dicarbaborane cluster with a specific CA IX hydrophobic patch containing V131 residue. The bulky side chain of F131 residue in CA II alters the shape of the catalytic cavity, disrupting favourable interactions of the spherical dicarbaborane cluster.

PubMed: 32962427
DOI: 10.1080/14756366.2020.1816996

Experimental method

X-RAY DIFFRACTION (1.05 Å)