5WGP

Human Carbonic Anhydrase IX-mimic complexed with AceK

Summary for 5WGP

• Entry DOI: 10.2210/pdb5wgp/pdb
• Descriptor: Carbonic anhydrase 2, ZINC ION, Acesulfame, ... (4 entities in total)
• Functional Keywords: carbonic anhydrase, acesulfame, inhibitor, lyase
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm : P00918
• Total number of polymer chains: 1
• Total formula weight: 29399.33

Authors

Murray, A.B.,Lomelino, C.L.,Supuran, C.T.,McKenna, R. (deposition date: 2017-07-14, release date: 2018-02-07, Last modification date: 2024-03-13)

Primary citation

Murray, A.B.,Lomelino, C.L.,Supuran, C.T.,McKenna, R.
"Seriously Sweet": Acesulfame K Exhibits Selective Inhibition Using Alternative Binding Modes in Carbonic Anhydrase Isoforms.
J. Med. Chem., 61:1176-1181, 2018

PubMed Abstract: Human carbonic anhydrase IX (CA IX) is upregulated in neoplastic tissues; as such, it is studied as a drug target for anticancer chemotherapy. Inhibition of CA IX has been shown to be therapeutically favorable in terms of reducing tumor growth. Previously, saccharin, a commonly used artificial sweetener, has been observed to selectively inhibit CA IX over other CA isoforms. In this study, X-ray crystallography showed acesulfame potassium (Ace K) binding directly to the catalytic zinc in CA IX (mimic) and through a bridging water in CA II. This modulation in binding is reflected in the binding constants, with Ace K inhibiting CA IX but not other CA isoforms. Hence, this study establishes the potential of Ace K (an FDA approved food additive) as a lead compound in the design and development of CA IX specific inhibitors.

PubMed: 29266943
DOI: 10.1021/acs.jmedchem.7b01470

Experimental method

X-RAY DIFFRACTION (1.53 Å)