6Z04
Nido-carborane butyl-sulfonamide in complex with CA IX mimic
Summary for 6Z04
| Entry DOI | 10.2210/pdb6z04/pdb |
| Related | 6YZJ 6YZK 6YZL 6YZM 6YZN 6YZO 6YZP 6YZQ 6YZR 6YZS 6YZT 6YZU 6YZV 6YZW 6YZX |
| Descriptor | Carbonic anhydrase 2, ZINC ION, Carborane nido-butyl-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 | 29523.81 |
| 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 Cited by 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: 32962427DOI: 10.1080/14756366.2020.1816996 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.05 Å) |
Structure validation
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