4ZX1
Engineered Carbonic Anhydrase IX mimic in complex with a glucosyl sulfamate inhibitor
Summary for 4ZX1
| Entry DOI | 10.2210/pdb4zx1/pdb |
| Related | 4ZWX 4ZWY 4ZWZ 4ZX0 |
| Descriptor | Carbonic anhydrase 2, ZINC ION, DIMETHYL SULFOXIDE, ... (5 entities in total) |
| Functional Keywords | carbonic anhydrase ix mimic, glucosyl sulfamate, inhibitor complex., 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 | 29513.62 |
| Authors | Mahon, B.P.,Lomelino, C.L.,Salguero, A.L.,McKenna, R. (deposition date: 2015-05-20, release date: 2015-10-28, Last modification date: 2024-03-06) |
| Primary citation | Mahon, B.P.,Lomelino, C.L.,Moeker, J.,Rankin, G.M.,Driscoll, J.M.,Salguero, A.L.,Pinard, M.A.,Vullo, D.,Supuran, C.T.,Poulsen, S.A.,McKenna, R. Mapping Selective Inhibition of the Cancer-Related Carbonic Anhydrase IX using Structure-Activity Relationships of Glucosyl-Based Sulfamates J. Med. Chem., 58:6630-6638, 2015 Cited by PubMed Abstract: Inhibition of human carbonic anhydrase IX (hCA IX) has shown to be therapeutically advantageous for treating many types of highly aggressive cancers. However, designing selective inhibitors for hCA IX has been difficult due to its high structural homology and sequence similarity with off-target hCAs. Recently, the use of glucosyl sulfamate inhibitors has shown promise as selective inhibitors for hCA IX. In this study, we present five X-ray crystal structures, determined to a resolution of 1.7 Å or better, of both hCA II (a ubiquitous CA) and an engineered hCA IX-mimic in complex with selected glucosyl sulfamates and structurally rationalize mechanisms for hCA IX selectivity. Results from this study have allowed us, for the first time, to empirically "map" key interactions of the hCA IX active site in order to establish parameters needed to design novel hCA IX selective inhibitors. PubMed: 26203869DOI: 10.1021/acs.jmedchem.5b00845 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.501 Å) |
Structure validation
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