{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T22:43:44Z","timestamp":1790117024928,"version":"4.0.1"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2008,12,31]],"date-time":"2008-12-31T00:00:00Z","timestamp":1230681600000},"content-version":"vor","delay-in-days":5478,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"NSF","award":["DIR-8821184"],"award-info":[{"award-number":["DIR-8821184"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Protein Science"],"published-print":{"date-parts":[[1994,1]]},"abstract":"Abstract<\/jats:title>\n \n The 3\u2010dimensional structure of human carbonic anhydrase II (HCAII; EC 4.2.1.1) complexed with 3 structurally related inhibitors,\n la, lb<\/jats:italic>\n , and\n lc<\/jats:italic>\n , has been determined by X\u2010ray crystallographic methods. The 3 inhibitors (\n la<\/jats:italic>\n = C\n 8<\/jats:sub>\n H\n 12<\/jats:sub>\n N\n 2<\/jats:sub>\n O\n 4<\/jats:sub>\n S\n 3<\/jats:sub>\n ) vary only in the length of the substituent on the 4\u2010amino group:\n la<\/jats:italic>\n , proton;\n lb<\/jats:italic>\n , methyl; and\n lc<\/jats:italic>\n , ethyl. The binding constants (\n \n K\n i<\/jats:sub>\n <\/jats:italic>\n 's) for\n la, Ib<\/jats:italic>\n , and\n lc<\/jats:italic>\n to HCAII are 1.52, 1.88, and 0.37 nM, respectively. These structures were solved to learn if any structural cause could be found for the difference in binding. In the complex with inhibitors\n la<\/jats:italic>\n and\n lb<\/jats:italic>\n , electron density can be observed for His\u201064 and a bound water molecule in the native positions. When inhibitor\n lc<\/jats:italic>\n is bound, the side chain attached to the 4\u2010amino group is positioned so that His\u201064 can only occupy the alternate position and the bound water is absent. While a variety of factors contribute to the observed binding constants, the major reason\n lc<\/jats:italic>\n binds tighter to HCAII than does\n la<\/jats:italic>\n or\n lb<\/jats:italic>\n appears to be entropy: the increase in entropy when the bound water molecule is released contributes to the increase in binding and overcomes the small penalty for putting the His\u201064 side chain in a higher energy state.\n <\/jats:p>","DOI":"10.1002\/pro.5560030115","type":"journal-article","created":{"date-parts":[[2010,7,12]],"date-time":"2010-07-12T04:35:04Z","timestamp":1278909304000},"page":"118-125","source":"Crossref","is-referenced-by-count":64,"title":["Positions of His\u201064 and a bound water in human carbonic anhydrase II upon binding three structurally related inhibitors"],"prefix":"10.1002","volume":"3","author":[{"given":"Graham M.","family":"Smith","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard S","family":"Alexander","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David W.","family":"Christianson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian M.","family":"Mckeever","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald S.","family":"Ponticello","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"Springer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William C.","family":"Randall","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John J.","family":"Baldwin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles N.","family":"Habecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2008,12,31]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/ar00089a001"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00132a003"},{"key":"e_1_2_1_4_1","first-page":"1","article-title":"Scientists from Merck and Vertex describe role of X\u2010ray crystallography in drug design","volume":"7","author":"Baldwin JJ","year":"1992","journal-title":"Chem Design Automation News"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(77)80200-3"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00269a052"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0108767390002355"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.340040406"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0076-6879(85)15021-4"},{"key":"e_1_2_1_10_1","volume-title":"A guide to macromolecular X\u2010ray data reduction for the Siemens area detector system: The XENGEN system, version2.0","author":"Howard A J","year":"1990"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-2836(83)90008-6"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.79.20.6137"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470122884.ch4"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00102a005"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/newbio235131a0"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0365110X52002161"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1967.47.4.595"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00025a005"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(75)90434-0"},{"key":"e_1_2_1_20_1","first-page":"149","article-title":"Carbonic anhydrase: Structure, catalytic versatility, and inhibition","volume":"47","author":"Pocker Y","year":"1978","journal-title":"Adv Enzymol Relat Areas Mol Biol"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00387a002"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00110a008"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00381a001"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0263-7855(98)80040-4"},{"key":"e_1_2_1_25_1","unstructured":"SteigemannW.1974. Die Entwicklung und Anwendung von Rechenverfahren und Rechenprogrammen zur Strukturanalyse von Proteinem am Beispiel des trypsin\u2010trypsininhibitor Komplexes des freien Inhibitors und der L\u2010Asparaginase [thesis]. Munchen: Technische Universit\u00e4t."},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi00445a054"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm00113a005"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/150152a0"}],"container-title":["Protein Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpro.5560030115","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fpro.5560030115","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pro.5560030115","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T03:41:22Z","timestamp":1698118882000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pro.5560030115"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,1]]},"references-count":27,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1994,1]]}},"alternative-id":["10.1002\/pro.5560030115"],"URL":"https:\/\/doi.org\/10.1002\/pro.5560030115","archive":["Portico"],"relation":{},"ISSN":["0961-8368","1469-896X"],"issn-type":[{"value":"0961-8368","type":"print"},{"value":"1469-896X","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,1]]}}}