carbonic anhydrase 4

Target id: 2599

Nomenclature: carbonic anhydrase 4

Family: 4.2.1.1 Carbonate dehydratases

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for carbonic anhydrase 4 in GtoImmuPdb

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 312 17q23.1 CA4 carbonic anhydrase 4
Mouse - 305 11 C Car4 carbonic anhydrase 4
Rat - 309 10q26 Car4 carbonic anhydrase 4
Previous and Unofficial Names
CAIV | Car4 | carbonic anhydrase IV
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
GenitoUrinary Development Molecular Anatomy Project
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
Orphanet
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Enzyme Reaction
EC Number: 4.2.1.1

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
methazolamide Hs Inhibition 7.6 pKi 2
pKi 7.6 (Ki 2.4x10-8 M) [2]
topiramate Hs Inhibition 7.4 pKi 2
pKi 7.4 (Ki 4.3x10-8 M) [2]
acetazolamide Hs Inhibition 7.1 – 7.6 pKi 1,4
pKi 7.1 – 7.6 (Ki 7.4x10-8 – 2.5x10-8 M) [1,4]
chlorthalidone Hs Inhibition 6.7 pKi 3
pKi 6.7 (Ki 1.96x10-7 M) [3]
diclofenamide Hs Inhibition 4.8 pKi 5
pKi 4.8 (Ki 1.5x10-5 M) [5]
Inhibitor Comments
Acetazolamide inhibits carbonic anhydrases I, IV and XIV, but has 10-fold lower affinity for XIV.Bbr>Methazolamide inhibits carbonic anhydrases I, IV and XIV with similar affinity.
Chlorthalidone is an approved drug inhibitor of carbonic anhydrase activity. We have tagged CA VII and XII as the primary targets for this drug as affinity is highest at these two isozymes [3].
Clinically-Relevant Mutations and Pathophysiology
Disease:  Retinitis pigmentosa 17; RP17
Synonyms: Retinitis pigmentosa [Orphanet: ORPHA791] [Disease Ontology: DOID:10584]
Disease Ontology: DOID:10584
OMIM: 600852
Orphanet: ORPHA791

References

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1. Avvaru BS, Wagner JM, Maresca A, Scozzafava A, Robbins AH, Supuran CT, McKenna R. (2010) Carbonic anhydrase inhibitors. The X-ray crystal structure of human isoform II in adduct with an adamantyl analogue of acetazolamide resides in a less utilized binding pocket than most hydrophobic inhibitors. Bioorg. Med. Chem. Lett.20 (15): 4376-81. [PMID:20605094]

2. Nishimori I, Vullo D, Innocenti A, Scozzafava A, Mastrolorenzo A, Supuran CT. (2005) Carbonic anhydrase inhibitors: inhibition of the transmembrane isozyme XIV with sulfonamides. Bioorg. Med. Chem. Lett.15 (17): 3828-33. [PMID:16039848]

3. Temperini C, Cecchi A, Scozzafava A, Supuran CT. (2009) Carbonic anhydrase inhibitors. Comparison of chlorthalidone, indapamide, trichloromethiazide, and furosemide X-ray crystal structures in adducts with isozyme II, when several water molecules make the difference. Bioorg. Med. Chem.17 (3): 1214-21. [PMID:19119014]

4. Turkmen H, Durgun M, Yilmaztekin S, Emul M, Innocenti A, Vullo D, Scozzafava A, Supuran CT. (2005) Carbonic anhydrase inhibitors. Novel sulfanilamide/acetazolamide derivatives obtained by the tail approach and their interaction with the cytosolic isozymes I and II, and the tumor-associated isozyme IX. Bioorg. Med. Chem. Lett.15 (2): 367-72. [PMID:15603956]

5. Winum JY, Temperini C, El Cheikh K, Innocenti A, Vullo D, Ciattini S, Montero JL, Scozzafava A, Supuran CT. (2006) Carbonic anhydrase inhibitors: clash with Ala65 as a means for designing inhibitors with low affinity for the ubiquitous isozyme II, exemplified by the crystal structure of the topiramate sulfamide analogue. J. Med. Chem.49 (24): 7024-31. [PMID:17125255]

How to cite this page

4.2.1.1 Carbonate dehydratases: carbonic anhydrase 4. Last modified on 30/03/2016. Accessed on 11/12/2017. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2599.