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The majority of normal functioning cells exhibit low-level expression of CA IX. However, in cancer cells CA IX is upregulated as a consequence of a metabolic transition known as the Warburg effect. The upregulation of CA IX for cancer progression has drawn interest in it being a potential therapeutic target. CA IX is a transmembrane protein, and its purification, yield and crystallization have proven challenging to structure-based drug design, whereas the closely related cytosolic soluble isoform CA II can be expressed and crystallized with ease. Therefore, we have utilized structural alignments and site-directed mutagenesis to engineer a CA II that mimics the active site of CA IX. In this paper, the X-ray crystal structure of this CA IX mimic in complex with sucrose is presented and has been refined to a resolution of 1.5\u2005\u00c5, an <jats:italic>R<\/jats:italic>\n                  <jats:sub>cryst<\/jats:sub> of 18.0% and an <jats:italic>R<\/jats:italic>\n                  <jats:sub>free<\/jats:sub> of 21.2%. The binding of sucrose at the entrance to the active site of the CA IX mimic, and not CA II, in a non-inhibitory mechanism provides a novel carbohydrate moiety binding site that could be further exploited to design isoform-specific inhibitors of CA IX.<\/jats:p>","DOI":"10.1107\/s2053230x1501239x","type":"journal-article","created":{"date-parts":[[2015,9,23]],"date-time":"2015-09-23T16:09:46Z","timestamp":1443024586000},"page":"1352-1358","update-policy":"https:\/\/doi.org\/10.1107\/cm_01","source":"Crossref","is-referenced-by-count":26,"title":["A sucrose-binding site provides a lead towards an isoform-specific inhibitor of the cancer-associated enzyme carbonic anhydrase IX"],"prefix":"10.1107","volume":"71","author":[{"given":"Melissa A.","family":"Pinard","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mayank","family":"Aggarwal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian P.","family":"Mahon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chingkuang","family":"Tu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"McKenna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"329","published-online":{"date-parts":[[2015,9,23]]},"reference":[{"key":"no5083_bb1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1107\/S0907444909052925","volume":"66","author":"Adams","year":"2010","journal-title":"Acta Cryst. 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