{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T17:19:11Z","timestamp":1771003151360,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,2,3]],"date-time":"2004-02-03T00:00:00Z","timestamp":1075766400000},"content-version":"vor","delay-in-days":5877,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Proteins"],"published-print":{"date-parts":[[1988,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The binding of four inhibitors\u2014mercuric ion, 3\u2010acetoxymercuri\u20104\u2010aminobenzenesulfonamide (AMS), acetazolamide (Diamox), and thiocyanate ion\u2014to human carbonic anhydrase II (HCA II) has been studied with X\u2010ray crystallography.<\/jats:p><jats:p>The binding of mercury to HCA II at pH 7.0 has been investigated at 3.1 \u00c5 resolution. Mercuric ions are observed at both nitrogens in the His\u201064 ring. One of these sites is pointing toward the zinc ion. The only other binding site for mercury is at Cys\u2010206.<\/jats:p><jats:p>The binding of the two sulfonamide inhibitors AMS and Diamox, has been reinvestigated at 2.0 and 3.0 \u00c5, respectively. Only the nitrogen of the sulfonamide group binds to the zinc ion replacing the hydroxyl ion. The sulfonamide oxygen closet to the zinc ion is 3.1 \u00c5 away. Thus the tetrahedral geometry of the zinc is retained, refuting earlier models of a pentacoordinated zinc.<\/jats:p><jats:p>The structure of the thiocyanate complex has been investigated at pH 8.5 and the structure has been refined at 1.9 \u00c5 resolution using the least\u2010squares refinement program PROLSQ. The crystallographic <jats:italic>R<\/jats:italic> factor is 17.6%. The zinc ion is pentacoordinated with the anion as well as a water molecule bound in addition to the three histidine residues. The nitrogen atom of the SCN<jats:sup>\u2212<\/jats:sup> ion is 1.9 \u00c5 from the zinc ion but shifted 1.3 \u00c5 with respect to the hydroxyl ion in the native structure and at van der Waals' distance from the O\u03b3l atom of Thr\u2010199. This is due to the inability of the O\u03b3l atom of Thr\u2010199 to serve as a hydrogen bond donor, thus repelling the nonprotonated nitrogen. The SCN<jats:sup>\u2212<\/jats:sup> molecule reaches into the deep end of the active site cavity where the sulfur atom has displaced the so\u2010called \u201cdeep\u201d water molecule of the native enzyme. The zinc\u2010bound water molecule is 2.2 \u00c5 from the zinc ion and 2.4 \u00c5 from the SCN<jats:sup>\u2212<\/jats:sup> nitrogen. In addition, this water is hydrogen bonded to the O\u03b3l atom of Thr\u2010199 and to another water molecule.<\/jats:p><jats:p>We have observed that solvent and inhibitor molecules have three possible binding sites on the zinc ion and their significance for the catalysis and inhibition of HCA II will be discussed. All available crystallographic data are consistent with a proposed catalytic mechanism in which both the OH moiety and one oxygen of the substrate HCO<jats:sub>3<\/jats:sub><jats:sup>\u2212<\/jats:sup> ion are ligated to the zinc ion.<\/jats:p>","DOI":"10.1002\/prot.340040407","type":"journal-article","created":{"date-parts":[[2005,5,29]],"date-time":"2005-05-29T01:01:04Z","timestamp":1117328464000},"page":"283-293","source":"Crossref","is-referenced-by-count":153,"title":["Crystallographic studies of inhibitor binding sites in human carbonic anhydrase II: A pentacoordinated binding of the SCN<sup>\u2212<\/sup> ion to the zinc at high pH"],"prefix":"10.1002","volume":"4","author":[{"given":"A. Elisabeth","family":"Eriksson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Per M.","family":"Kylsten","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T. Alwyn","family":"Jones","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anders","family":"Liljas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,2,3]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.1984.tb12315.x"},{"key":"e_1_2_1_3_2","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1007\/978-1-349-03230-3_4","volume-title":"Drug Action at the Molecular Level","author":"Kannan K. 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Chem."},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(65)80324-2"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(76)90072-3"},{"key":"e_1_2_1_14_2","unstructured":"Steigemann W.Die Entwicklung und Anwendung von Rechenverfahren und Rechenprogrammen zur Strukturanalyse von Proteiner am Biespiel des Trypsininhibitor Komplexes des freien Inhibitors und der L\u2010Asparaginase. Ph.D. thesis Technical University Munich 1974."},{"key":"e_1_2_1_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/newbio235131a0"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(69)90383-0"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889878013308"},{"key":"e_1_2_1_18_2","first-page":"303","volume-title":"Computational Crystallography","author":"Jones T. A.","year":"1982"},{"key":"e_1_2_1_19_2","first-page":"363","volume-title":"Oxygen Affinity of Hemoglobin and Red Cell Acid\u2010Base Status","author":"Bergst\u00e9n P.\u2010C.","year":"1971"},{"key":"e_1_2_1_20_2","first-page":"13.01","volume-title":"Computing in Crystallography","author":"Hendrickson W. A.","year":"1980"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0021889879012218"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1107\/S0567739481001587"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00520a022"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00280a011"},{"key":"e_1_2_1_25_2","doi-asserted-by":"crossref","first-page":"5813","DOI":"10.1016\/S0021-9258(18)99374-9","article-title":"Combination of bovine carbonic anhydrase with a fluorescent sulfonamide","volume":"242","author":"Chen R. F.","year":"1967","journal-title":"J. Biol. Chem."},{"key":"e_1_2_1_26_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1975.tb02449.x"},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0014-5793(88)81156-6"},{"key":"e_1_2_1_28_2","doi-asserted-by":"publisher","DOI":"10.1021\/ar00092a002"},{"key":"e_1_2_1_29_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja00360a009"},{"key":"e_1_2_1_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(83)80024-2"},{"key":"e_1_2_1_31_2","first-page":"155","volume-title":"Zinc Enzymes","author":"Rees D. C.","year":"1986"},{"key":"e_1_2_1_32_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00527a026"},{"key":"e_1_2_1_33_2","first-page":"115","article-title":"Structure and function of carbonic anhydrases","volume":"73","author":"Kannan K. K.","year":"1977","journal-title":"Imidazole binding to human carbonic anhydrase B and the mechanism of action of carbonic anhydrases. 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