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2wd3, resolution 1.80Å ()
Ligands: ,
Activity: Carbonate dehydratase, with EC number
Related: 1okl, 1i9q, 1zfq, 1if7, 1cam, 1t9n, 1cnw, 1okn, 1f2w, 1g52, 2h4n, 1bnm, 1cnh, 1bnq, 1ugc, 1xev, 1ugg, 1if9, 1g53, 1fqm, 1ca2, 1cal, 1fql, 1i9n, 1g4o, 2cba, 1ydc, 1ccs, 1lzv, 1bnv, 1fqr, 1rzb, 1a42, 1th9, 1zsb, 1cnb, 1hed, 1i8z, 1g48, 1lg5, 1bv3, 1g0f, 1tg3, 1cvc, 1ugd, 1i90, 1yo0, 1fsn, 1hva, 1rze, 1ugb, 1z9y, 2fmz, 1cnk, 1bn1, 1teq, 1rza, 2vvb, 1ccu, 1i9l, 2cbc, 1g46, 1cvb, 1cao, 1fsq, 6ca2, 5ca2, 1g1d, 1caj, 1cvf, 2fou, 1lgd, 1if6, 1bn4, 1teu, 1cra, 1ze8, 1if4, 1hea, 1hca, 1cah, 1g4j, 1raz, 1kwq, 1cim, 1cvh, 1if8, 1cin, 1i9m, 1zfk, 1fqn, 1zsa, 1lg6, 1cnc, 1bnn, 1uga, 2foq, 1tb0, 1cai, 2ax2, 1dcb, 1cnx, 2hd6, 5cac, 4cac, 1ttm, 1cak, 1i9o, 1cni, 1can, 2eu3, 1yda, 2wd2, 1yo2, 1eou, 1mua, 2ca2, 1cct, 2abe, 1oq5, 1rzc, 1ugf, 2cbe, 1thk, 1kwr, 1zgf, 1cay, 1moo, 1cng, 1hec, 2ez7, 8ca2, 9ca2, 1fr7, 1zh9, 1ydd, 1bic, 1lug, 1caz, 1cvd, 7ca2, 1fr4, 1cil, 4ca2, 2geh, 1g45, 1ydb, 1dca, 1fsr, 2cbb, 1i9p, 12ca, 1avn, 1bcd, 1am6, 1i91, 1cve, 1g3z, 1heb, 2cbd, 1zsc, 3ca2, 1bnu, 1zge, 1bnw, 2fov, 1te3, 1bnt, 1if5, 1yo1, 1rzd, 1g54, 1uge, 1g0e, 2fmg, 1ray, 1cva, 1ca3, 2eu2, 1tg9, 1tbt, 1xeg, 1bn3, 1okm, 1cny, 1cnj, 1h9n, 2vva, 2aw1, 1h4n, 2fos, 1h9q
Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml



Publication Abstract from PubMed

Single agents against multiple drug targets are of increasing interest. Hormone-dependent breast cancer (HDBC) may be more effectively treated by dual inhibition of aromatase and steroid sulfatase (STS). The aromatase inhibitory pharmacophore was thus introduced into a known biphenyl STS inhibitor to give a series of novel dual aromatase-sulfatase inhibitors (DASIs). Several compounds are good aromatase or STS inhibitors and DASI 20 (IC(50): aromatase, 2.0 nM; STS, 35 nM) and its chlorinated congener 23 (IC(50): aromatase, 0.5 nM; STS, 5.5 nM) are examples that show exceptional dual potency in JEG-3 cells. Both biphenyls share a para-sulfamate-containing ring B and a ring A, which contains a triazol-1-ylmethyl meta to the biphenyl bridge and para to a nitrile. At 1 mg/kg po, 20 and 23 reduced plasma estradiol levels strongly and inhibited liver STS activity potently in vivo. 23 is nonestrogenic and potently inhibits carbonic anhydrase II (IC(50) 86 nM). A complex was crystallized and its structure was solved by X-ray crystallography. This class of DASI should encourage further development toward multitargeted therapeutic intervention in HDBC.

Highly Potent First Examples of Dual Aromatase-Steroid Sulfatase Inhibitors based on a Biphenyl Template (dagger)., Woo LW, Jackson T, Putey A, Cozier G, Leonard P, Acharya KR, Chander SK, Purohit A, Reed MJ, Potter BV, J Med Chem. 2010 Feb 11. PMID:20148564

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


[CAH2_HUMAN] Defects in CA2 are the cause of osteopetrosis autosomal recessive type 3 (OPTB3) [MIM:259730]; also known as osteopetrosis with renal tubular acidosis, carbonic anhydrase II deficiency syndrome, Guibaud-Vainsel syndrome or marble brain disease. Osteopetrosis is a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. The disorder occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Autosomal recessive osteopetrosis is usually associated with normal or elevated amount of non-functional osteoclasts. OPTB3 is associated with renal tubular acidosis, cerebral calcification (marble brain disease) and in some cases with mental retardation.[1][2][3][4][5]


[CAH2_HUMAN] Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye.[6][7]

About this Structure

2wd3 is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

See Also


  • Woo LW, Jackson T, Putey A, Cozier G, Leonard P, Acharya KR, Chander SK, Purohit A, Reed MJ, Potter BV. Highly Potent First Examples of Dual Aromatase-Steroid Sulfatase Inhibitors based on a Biphenyl Template (dagger). J Med Chem. 2010 Feb 11. PMID:20148564 doi:10.1021/jm901705h
  1. Venta PJ, Welty RJ, Johnson TM, Sly WS, Tashian RE. Carbonic anhydrase II deficiency syndrome in a Belgian family is caused by a point mutation at an invariant histidine residue (107 His----Tyr): complete structure of the normal human CA II gene. Am J Hum Genet. 1991 Nov;49(5):1082-90. PMID:1928091
  2. Roth DE, Venta PJ, Tashian RE, Sly WS. Molecular basis of human carbonic anhydrase II deficiency. Proc Natl Acad Sci U S A. 1992 Mar 1;89(5):1804-8. PMID:1542674
  3. Soda H, Yukizane S, Yoshida I, Koga Y, Aramaki S, Kato H. A point mutation in exon 3 (His 107-->Tyr) in two unrelated Japanese patients with carbonic anhydrase II deficiency with central nervous system involvement. Hum Genet. 1996 Apr;97(4):435-7. PMID:8834238
  4. Hu PY, Lim EJ, Ciccolella J, Strisciuglio P, Sly WS. Seven novel mutations in carbonic anhydrase II deficiency syndrome identified by SSCP and direct sequencing analysis. Hum Mutat. 1997;9(5):383-7. PMID:9143915 doi:<383::AID-HUMU1>3.0.CO;2-5 10.1002/(SICI)1098-1004(1997)9:5<383::AID-HUMU1>3.0.CO;2-5
  5. Shah GN, Bonapace G, Hu PY, Strisciuglio P, Sly WS. Carbonic anhydrase II deficiency syndrome (osteopetrosis with renal tubular acidosis and brain calcification): novel mutations in CA2 identified by direct sequencing expand the opportunity for genotype-phenotype correlation. Hum Mutat. 2004 Sep;24(3):272. PMID:15300855 doi:10.1002/humu.9266
  6. Briganti F, Mangani S, Scozzafava A, Vernaglione G, Supuran CT. Carbonic anhydrase catalyzes cyanamide hydration to urea: is it mimicking the physiological reaction? J Biol Inorg Chem. 1999 Oct;4(5):528-36. PMID:10550681
  7. Kim CY, Whittington DA, Chang JS, Liao J, May JA, Christianson DW. Structural aspects of isozyme selectivity in the binding of inhibitors to carbonic anhydrases II and IV. J Med Chem. 2002 Feb 14;45(4):888-93. PMID:11831900

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