ArticleActa crystallographica. Section F, Structural biology communications2015
A sucrose-binding site provides a lead towards an isoform-specific inhibitor of the cancer-associated enzyme carbonic anhydrase IX.
Article in Acta crystallographica. Section F, Structural biology communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Disruption of the Physical Interaction Between Carbonic Anhydrase IX and the Monocarboxylate Transporter 4 Impacts Lactate Transport in Breast Cancer Cells.International journal of molecular sciences · 2024Article
- Lasamide, a Potent Human Carbonic Anhydrase Inhibitor from the Market: Inhibition Profiling and Crystallographic Studies.ACS medicinal chemistry letters · 2024Article
- Design and synthesis of chromene-1,2,3-triazole benzene sulfonamide hybrids as potent carbonic anhydrase-IX inhibitors against prostate cancer.RSC medicinal chemistry · 2024Article
- Article
- The Anticancer Activity for the Bumetanide-Based Analogs via Targeting the Tumor-Associated Membrane-Bound Human Carbonic Anhydrase-IX Enzyme.Pharmaceuticals (Basel, Switzerland) · 2020Article
- Biophysical Characterization of Cancer-Related Carbonic Anhydrase IX.International journal of molecular sciences · 2020Article
- Engineered Carbonic Anhydrase VI-Mimic Enzyme Switched the Structure and Affinities of Inhibitors.Scientific reports · 2019Article
- Synthesis of saccharin-glycoconjugates targeting carbonic anhydrase using a one-pot cyclization/deprotection strategy.Carbohydrate research · 2019Article
- Sweet Binders: Carbonic Anhydrase IX in Complex with Sucralose.ACS medicinal chemistry letters · 2018Article
- Cancer Drug Development of Carbonic Anhydrase Inhibitors beyond the Active Site.Molecules (Basel, Switzerland) · 2018Review
- Crystallography and Its Impact on Carbonic Anhydrase Research.International journal of medicinal chemistry · 2018Review
- The Structure of Carbonic Anhydrase IX Is Adapted for Low-pH Catalysis.Biochemistry · 2016Article
- Observed surface lysine acetylation of human carbonic anhydrase II expressed in Escherichia coli.Protein science : a publication of the Protein Society · 2015Article
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5 authors.
Funding
Abstract
Human carbonic anhydrase (CA; EC 4.2.1.1) isoform IX (CA IX) is an extracellular zinc metalloenzyme that catalyzes the reversible hydration of CO2 to HCO3(-), thereby playing a role in pH regulation. 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 Å, an Rcryst of 18.0% and an Rfree 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.
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