4RIU

A Carbonic Anhydrase IX Mimic in Complex with a Saccharin-Based Inhibitor

Summary for 4RIU

• Entry DOI: 10.2210/pdb4riu/pdb
• Related: 4RIV
• Descriptor: Carbonic anhydrase 2, ZINC ION, GLYCEROL, ... (5 entities in total)
• Functional Keywords: carbonic anhydrase fold, reversible hydration of co2, active site point mutations, cytosolic, 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: 29984.98

Authors

Mahon, B.P.,McKenna, R. (deposition date: 2014-10-07, release date: 2015-02-04, Last modification date: 2023-09-20)

Primary citation

Mahon, B.P.,Hendon, A.M.,Driscoll, J.M.,Rankin, G.M.,Poulsen, S.A.,Supuran, C.T.,McKenna, R.
Saccharin: A lead compound for structure-based drug design of carbonic anhydrase IX inhibitors.
Bioorg.Med.Chem., 23:849-854, 2015

PubMed Abstract: Carbonic anhydrase IX (CA IX) is a key modulator of aggressive tumor behavior and a prognostic marker and target for several cancers. Saccharin (SAC) based compounds may provide an avenue to overcome CA isoform specificity, as they display both nanomolar affinity and preferential binding, for CA IX compared to CA II (>50-fold for SAC and >1000-fold when SAC is conjugated to a carbohydrate moiety). The X-ray crystal structures of SAC and a SAC-carbohydrate conjugate bound to a CA IX-mimic are presented and compared to CA II. The structures provide substantial new insight into the mechanism of SAC selective CA isoform inhibition.

PubMed: 25614109
DOI: 10.1016/j.bmc.2014.12.030

Experimental method

X-RAY DIFFRACTION (1.651 Å)