ArticleProceedings of the National Academy of Sciences of the United States of America1996
Crystal structure of the secretory form of membrane-associated human carbonic anhydrase IV at 2.8-A resolution.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 144 citations in OpenAlex.
- CA-IV-directed small-molecule shuttle enables targeted brain delivery of biologics.Nature chemical biology · 2026Article
- Computational Approaches and Structure-Based Drug Design of CAIs.Sub-cellular biochemistry · 2026Review
- The amazing AAV capsids: Into the structure-verse.Molecular therapy. Methods & clinical development · 2025Review
- Article
- Generating functional and multistate proteins with a multimodal diffusion transformer.bioRxiv : the preprint server for biology · 2025Article
- Exploration of Aromatic Hydrazides as Inhibitors of Human Carbonic Anhydrases.Archiv der Pharmazie · 2025Article
- Structural basis of the recognition of adeno-associated virus by the neurological system-related receptor carbonic anhydrase IV.PLoS pathogens · 2024Article
- Antihistamines, phenothiazine-based antipsychotics, and tricyclic antidepressants potently activate pharmacologically relevant human carbonic anhydrase isoforms II and VII.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Carbonic anhydrase IV in lizard chemical signals.Scientific reports · 2023Article
- Evaluation of tea (Camellia sinensis L.) phytochemicals as multi-disease modulators, a multidimensional in silico strategy with the combinations of network pharmacology, pharmacophore analysis, statistics and molecular docking.Molecular diversity · 2023Article
- Carbonic Anhydrases as Potential Targets Against Neurovascular Unit Dysfunction in Alzheimer's Disease and Stroke.Frontiers in aging neuroscience · 2021Review
- Human carbonic anhydrases and post-translational modifications: a hidden world possibly affecting protein properties and functions.Journal of enzyme inhibition and medicinal chemistry · 2020Review
- Alpha-Carbonic Anhydrases from Hydrothermal Vent Sources as Potential Carbon Dioxide Sequestration Agents:International journal of molecular sciences · 2020Article
- Sulfonamide Inhibitors of Human Carbonic Anhydrases Designed through a Three-Tails Approach: Improving Ligand/Isoform Matching and Selectivity of Action.Journal of medicinal chemistry · 2020Article
- Exploration of the residues modulating the catalytic features of human carbonic anhydrase XIII by a site-specific mutagenesis approach.Journal of enzyme inhibition and medicinal chemistry · 2019Article
- Carbonic anhydrases as disease markers.Expert opinion on therapeutic patents · 2019Review
- Membrane-anchored carbonic anhydrase IV interacts with monocarboxylate transporters via their chaperones CD147 and GP70.The Journal of biological chemistry · 2019Article
- Intrinsic thermodynamics of high affinity inhibitor binding to recombinant human carbonic anhydrase IV.European biophysics journal : EBJ · 2018Article
- Crystallography and Its Impact on Carbonic Anhydrase Research.International journal of medicinal chemistry · 2018Review
- Insights into the role of reactive sulfhydryl groups of Carbonic Anhydrase III and VII during oxidative damage.Journal of enzyme inhibition and medicinal chemistry · 2017Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
It has recently been demonstrated that the C-terminal deletion mutant of recombinant human carbonic anhydrase IV (G267X CA IV) converts the normally glycosylphosphatidylinositol-anchored enzyme into a soluble secretory form which has the same catalytic properties as the membrane-associated enzyme purified from human tissues. We have determined the three-dimensional structure of the secretory form of human CA IV by x-ray crystallographic methods to a resolution of 2.8 A. Although the zinc binding site and the hydrophobic substrate binding pocket of CA IV are generally similar to those of other mammalian isozymes, unique structural differences are found elsewhere in the active site. Two disufide linkages, Cys-6-Cys-11G and Cys-23-Cys-203, stabilize the conformation of the N-terminal domain. The latter disulfide additionally stabilizes an active site loop containing a cis-peptide linkage between Pro-201 and Thr-202 (this loop contains catalytic residue Thr-199). On the opposite side of the active site, the Val-131-Asp-136 segment adopts an extended loop conformation instead of an alpha-helix conformation as found in other isozymes. Finally, the C terminus is surrounded by a substantial electropositive surface potential, which is likely to stabilize the interaction of CA IV with the negatively charged phospholipid headgroups of the membrane. These structural features are unique to CA IV and provide a framework for the design of sulfonamide inhibitors selective for this particular isozyme.
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