4ht2

Crystal structure of human carbonic anhydrase isozyme XII with the inhibitor.Crystal structure of human carbonic anhydrase isozyme XII with the inhibitor.

Structural highlights

4ht2 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.45Å
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

CAH12_HUMAN Defects in CA12 are the cause of hyperchlorhidrosis isolated (HCHLH) [MIM:143860. HCHLH is a disorder characterized by excessive sweating and increased sweat chloride levels. Affected individuals suffer from episodes of hyponatremic dehydration and report increased amounts of visible salt precipitates in sweat.^[1]

Function

CAH12_HUMAN Reversible hydration of carbon dioxide.

Publication Abstract from PubMed

A series of 4-substituted-2,3,5,6-tetrafluorobenezenesulfonamides were synthesized and their binding potencies as inhibitors of recombinant human carbonic anhydrase isozymes I, II, VII, XII, and XIII were determined by the thermal shift assay, isothermal titration calorimetry, and stop-flow CO2 hydration assay. All fluorinated benzenesulfonamides exhibited nanomolar binding potency toward tested CAs and fluorinated benzenesulfonamides posessed higher binding potency than non-fluorinated compounds. The crystal structures of 4-[(4,6-dimethylpyrimidin-2-yl)thio]-2,3,5,6-tetrafluorobenzenesulfonamide in complex with CA II and CA XII, and 2,3,5,6-tetrafluoro-4-[(2-hydroxyethyl)sulfonyl]benzenesulfonamide in complex with CA XIII were determined. The observed dissociation constants for several fluorinated compounds reached subnanomolar range for CA I isozyme. The affinity and the selectivity of the compounds towards tested isozymes are presented.

4-Substituted-2,3,5,6-tetrafluorobenzenesulfonamides as inhibitors of carbonic anhydrases I, II, VII, XII, and XIII.,Dudutiene V, Zubriene A, Smirnov A, Gylyte J, Timm D, Manakova E, Grazulis S, Matulis D Bioorg Med Chem. 2013 Apr 1;21(7):2093-106. doi: 10.1016/j.bmc.2013.01.008. Epub , 2013 Jan 16. PMID:23394791^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Feldshtein M, Elkrinawi S, Yerushalmi B, Marcus B, Vullo D, Romi H, Ofir R, Landau D, Sivan S, Supuran CT, Birk OS. Hyperchlorhidrosis caused by homozygous mutation in CA12, encoding carbonic anhydrase XII. Am J Hum Genet. 2010 Nov 12;87(5):713-20. doi: 10.1016/j.ajhg.2010.10.008. Epub, 2010 Oct 28. PMID:21035102 doi:10.1016/j.ajhg.2010.10.008
↑ Dudutiene V, Zubriene A, Smirnov A, Gylyte J, Timm D, Manakova E, Grazulis S, Matulis D. 4-Substituted-2,3,5,6-tetrafluorobenzenesulfonamides as inhibitors of carbonic anhydrases I, II, VII, XII, and XIII. Bioorg Med Chem. 2013 Apr 1;21(7):2093-106. doi: 10.1016/j.bmc.2013.01.008. Epub , 2013 Jan 16. PMID:23394791 doi:http://dx.doi.org/10.1016/j.bmc.2013.01.008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] Feldshtein M, Elkrinawi S, Yerushalmi B, Marcus B, Vullo D, Romi H, Ofir R, Landau D, Sivan S, Supuran CT, Birk OS. Hyperchlorhidrosis caused by homozygous mutation in CA12, encoding carbonic anhydrase XII. Am J Hum Genet. 2010 Nov 12;87(5):713-20. doi: 10.1016/j.ajhg.2010.10.008. Epub, 2010 Oct 28. PMID:21035102 doi:10.1016/j.ajhg.2010.10.008

[2] Dudutiene V, Zubriene A, Smirnov A, Gylyte J, Timm D, Manakova E, Grazulis S, Matulis D. 4-Substituted-2,3,5,6-tetrafluorobenzenesulfonamides as inhibitors of carbonic anhydrases I, II, VII, XII, and XIII. Bioorg Med Chem. 2013 Apr 1;21(7):2093-106. doi: 10.1016/j.bmc.2013.01.008. Epub , 2013 Jan 16. PMID:23394791 doi:http://dx.doi.org/10.1016/j.bmc.2013.01.008

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