3fw3

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3fw3, resolution 1.72Å ()
Ligands: , , ,
Gene: CA4 (Homo sapiens)
Activity: Carbonate dehydratase, with EC number 4.2.1.1
Related: 3f7b, 3f7u
Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml


Contents

Crystal Structure of soluble domain of CA4 in complex with Dorzolamide

Publication Abstract from PubMed

A novel series of potent thioether benzenesulfonamide inhibitors of carbonic anhydrases II and IV was discovered using structure-based drug design. Synthesis, structure-activity relationship, and optimization of physicochemical properties are described. Low nanomolar potency was achieved, and selected compounds with improved thermodynamic solubility showed promising in vitro inhibition of carbonic anhydrase activity in rabbit iris ciliary body homogenate.

Thioether benzenesulfonamide inhibitors of carbonic anhydrases II and IV: structure-based drug design, synthesis, and biological evaluation., Vernier W, Chong W, Rewolinski D, Greasley S, Pauly T, Shaw M, Dinh D, Ferre RA, Nukui S, Ornelas M, Reyner E, Bioorg Med Chem. 2010 May 1;18(9):3307-19. Epub 2010 Mar 11. PMID:20363633

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

Disease

[CAH4_HUMAN] Defects in CA4 are the cause of retinitis pigmentosa type 17 (RP17) [MIM:600852]. RP leads to degeneration of retinal photoreceptor cells. Patients typically have night vision blindness and loss of midperipheral visual field. As their condition progresses, they lose their far peripheral visual field and eventually central vision as well. RP17 inheritance is autosomal dominant. Note=Defective acid overload removal from retina and retinal epithelium, due to mutant CA4, is responsible for photoreceptor degeneration, indicating that impaired pH homeostasis is the most likely cause underlying the RP17 phenotype.[1]

Function

[CAH4_HUMAN] Reversible hydration of carbon dioxide. May stimulate the sodium/bicarbonate transporter activity of SLC4A4 that acts in pH homeostasis. It is essential for acid overload removal from the retina and retina epithelium, and acid release in the choriocapillaris in the choroid.[2]

About this Structure

3fw3 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

See Also

Reference

  • Vernier W, Chong W, Rewolinski D, Greasley S, Pauly T, Shaw M, Dinh D, Ferre RA, Nukui S, Ornelas M, Reyner E. Thioether benzenesulfonamide inhibitors of carbonic anhydrases II and IV: structure-based drug design, synthesis, and biological evaluation. Bioorg Med Chem. 2010 May 1;18(9):3307-19. Epub 2010 Mar 11. PMID:20363633 doi:10.1016/j.bmc.2010.03.014
  1. Yang Z, Alvarez BV, Chakarova C, Jiang L, Karan G, Frederick JM, Zhao Y, Sauve Y, Li X, Zrenner E, Wissinger B, Hollander AI, Katz B, Baehr W, Cremers FP, Casey JR, Bhattacharya SS, Zhang K. Mutant carbonic anhydrase 4 impairs pH regulation and causes retinal photoreceptor degeneration. Hum Mol Genet. 2005 Jan 15;14(2):255-65. Epub 2004 Nov 24. PMID:15563508 doi:ddi023
  2. Yang Z, Alvarez BV, Chakarova C, Jiang L, Karan G, Frederick JM, Zhao Y, Sauve Y, Li X, Zrenner E, Wissinger B, Hollander AI, Katz B, Baehr W, Cremers FP, Casey JR, Bhattacharya SS, Zhang K. Mutant carbonic anhydrase 4 impairs pH regulation and causes retinal photoreceptor degeneration. Hum Mol Genet. 2005 Jan 15;14(2):255-65. Epub 2004 Nov 24. PMID:15563508 doi:ddi023

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