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2x7t, resolution 1.89Å ()
Ligands: , ,
Activity: Carbonate dehydratase, with EC number
Related: 1okl, 2wej, 1i9q, 1zfq, 1if7, 1cam, 1t9n, 1cnw, 1okn, 1f2w, 1g52, 2h4n, 1bnm, 1cnh, 1bnq, 1xev, 1ugc, 1ugg, 1if9, 1g53, 1fqm, 1ca2, 1cal, 1fql, 1i9n, 1g4o, 2cba, 1ydc, 1ccs, 1lzv, 1bnv, 1fqr, 1a42, 1rzb, 1th9, 1zsb, 1cnb, 1i8z, 1hed, 1g48, 1lg5, 1bv3, 1g0f, 1tg3, 1cvc, 1ugd, 1i90, 1yo0, 2wd3, 1hva, 1fsn, 1ugb, 1rze, 1z9y, 2fmz, 2weh, 1cnk, 1bn1, 1teq, 1rza, 2vvb, 1ccu, 1i9l, 2cbc, 1cvb, 1g46, 1cao, 1fsq, 6ca2, 5ca2, 1g1d, 1caj, 2fou, 1cvf, 1bn4, 1lgd, 1if6, 1teu, 1cra, 1if4, 1ze8, 1hea, 1cah, 1hca, 1g4j, 1kwq, 1raz, 1cim, 1cvh, 1if8, 1cin, 1i9m, 1zfk, 1zsa, 1fqn, 1lg6, 1cnc, 1uga, 1bnn, 2foq, 1tb0, 1cai, 2ax2, 1dcb, 1cnx, 1ttm, 4cac, 2hd6, 5cac, 1cak, 1i9o, 1cni, 1can, 1yda, 2eu3, 1eou, 1yo2, 2wd2, 1mua, 1cct, 2ca2, 1oq5, 2abe, 1ugf, 1rzc, 2cbe, 1thk, 1kwr, 1cay, 1zgf, 1moo, 1cng, 1hec, 2ez7, 8ca2, 9ca2, 1fr7, 1ydd, 1zh9, 1bic, 1lug, 1caz, 7ca2, 1cvd, 1fr4, 4ca2, 1cil, 2geh, 1g45, 1ydb, 2cbb, 1dca, 1fsr, 12ca, 1avn, 1i9p, 1bcd, 1am6, 1i91, 1cve, 1g3z, 1heb, 2cbd, 1zsc, 3ca2, 1bnu, 2weg, 1zge, 1bnw, 2fov, 1te3, 1bnt, 1if5, 2weo, 1yo1, 1g54, 1rzd, 1uge, 2fmg, 1g0e, 1ray, 1cva, 1ca3, 2eu2, 1tg9, 1tbt, 1xeg, 1bn3, 1cny, 1okm, 1cnj, 1h9n, 2vva, 2aw1, 1h4n, 2fos, 1h9q, 2x7s, 2x7u

Resources: FirstGlance, OCA, RCSB, PDBsum
Coordinates: save as pdb, mmCIF, xml



Publication Abstract from PubMed

Carbonic anhydrase (CA) catalyzes the reversible hydration of carbon dioxide to hydrogen carbonate, and its role in maintaining pH balance has made it an attractive drug target. Steroidal sulfamate esters, inhibitors of the cancer drug target steroid sulfatase (STS), are sequestered in vivo by CA II in red blood cells, which may be the origin of their excellent drug properties. Understanding the structural basis of this is important for drug design. Structures of CA II complexed with 2-methoxyestradiol 3-O-sulfamate (3), 2-ethylestradiol 3,17-O,O-bis(sulfamate) (4), and 2-methoxyestradiol 17-O-sulfamate (5) are reported to 2.10, 1.85, and 1.64 A, respectively. Inhibitor 3 interacts with the active site Zn(II) ion through the 3-O-sulfamate, while inhibitors 4 and 5 bind through their 17-O-sulfamate. Comparison of the IC(50) values for CA II inhibition gave respective values of 56, 662, 2113, 169, 770, and 86 nM for estrone 3-O-sulfamate (1), 2-methoxyestradiol 3,17-O,O-bis(sulfamate) (2), 3, 4, 5, and 5'-((4H-1,2,4-triazol-4-yl)methyl)-3-chloro-2'-cyanobiphenyl-4-yl sulfamate (6), a nonsteroidal dual aromatase-sulfatase inhibitor. Inhibitors 2, 5, and 6 showed binding to a second adjacent site that is capable of binding both steroidal and nonsteroidal ligands. Examination of both IC(50) values and crystal structures suggests that 2-substituents on the steroid nucleus hinder binding via a 3-O-sulfamate, leading to coordination through a 17-O-sulfamate if present. These results underline the influence of small structural changes on affinity and mode of binding, the degree of flexibility in the design of sulfamate-based inhibitors, and suggest a strategy for inhibitors which interact with both the active site and the second adjacent binding site simultaneously that could be both potent and selective.

Structures of Human Carbonic Anhydrase II/Inhibitor Complexes Reveal a Second Binding Site for Steroidal and Nonsteroidal Inhibitors (,)., Cozier GE, Leese MP, Lloyd MD, Baker MD, Thiyagarajan N, Acharya KR, Potter BV, Biochemistry. 2010 Mar 29. PMID:20297840

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

2x7t is a 1 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.

See Also


  • Cozier GE, Leese MP, Lloyd MD, Baker MD, Thiyagarajan N, Acharya KR, Potter BV. Structures of Human Carbonic Anhydrase II/Inhibitor Complexes Reveal a Second Binding Site for Steroidal and Nonsteroidal Inhibitors (,). Biochemistry. 2010 Mar 29. PMID:20297840 doi:10.1021/bi902178w
  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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