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The central role of CDKs in cell cycle regulation makes them a potential new target for inhibitory molecules with anti\u2010proliferative and\/or anti\u2010neoplastic effects. We describe the crystal structures of the complexes of CDK2 with a weakly specific CDK inhibitor, N6\u2010(\u03b42\u2010isopentenyl)adenine, and a strongly specific inhibitor, olomoucine. Both inhibitors are adenine derivatives and bind in the adenine binding pocket of CDK2, but in an unexpected and different orientation from the adenine of the authentic ligand ATP. The N6\u2010benzyl substituent in olomoucine binds outside the conserved binding pocket and is most likely responsible for its specificity. The structural information from the CDK2\u2010olomoucine complex will be useful in directing the search for the next generation inhibitors with improved properties. \u00a9 1995 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/prot.340220408","type":"journal-article","created":{"date-parts":[[2005,5,29]],"date-time":"2005-05-29T01:42:35Z","timestamp":1117330955000},"page":"378-391","source":"Crossref","is-referenced-by-count":233,"title":["Multiple modes of ligand recognition: Crystal structures of cyclin\u2010dependent protein kinase 2 in complex with ATP and two inhibitors, olomoucine and isopentenyladenine"],"prefix":"10.1002","volume":"22","author":[{"given":"Ursula","family":"Schulze\u2010Gahmen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeroen","family":"Brandsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather D.","family":"Jones","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David O.","family":"Morgan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurent","family":"Meijer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaroslav","family":"Vesely","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung\u2010Hou","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2004,2,3]]},"reference":[{"key":"e_1_2_1_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.61.070192.002301"},{"key":"e_1_2_1_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90360-O"},{"key":"e_1_2_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0955-0674(93)90101-U"},{"key":"e_1_2_1_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1991.tb04894.x"},{"key":"e_1_2_1_6_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.3.5.571"},{"key":"e_1_2_1_7_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.3.1.13"},{"key":"e_1_2_1_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1992.tb05493.x"},{"key":"e_1_2_1_9_2","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.4.1.79"},{"key":"e_1_2_1_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1991.tb04897.x"},{"key":"e_1_2_1_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1991.tb04896.x"},{"key":"e_1_2_1_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.7.2917"},{"key":"e_1_2_1_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1993.tb05633.x"},{"key":"e_1_2_1_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/366704a0"},{"key":"e_1_2_1_15_2","first-page":"436","article-title":"A cell cycle regulator potentially involved in genesis of many tumor types","volume":"264","author":"Kamb A.","year":"1994","journal-title":"Nature (London)"},{"key":"e_1_2_1_16_2","doi-asserted-by":"publisher","DOI":"10.1038\/368753a0"},{"key":"e_1_2_1_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90572-X"},{"key":"e_1_2_1_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90573-8"},{"key":"e_1_2_1_19_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.12.5291"},{"key":"e_1_2_1_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/366707a0"},{"key":"e_1_2_1_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/366701a0"},{"key":"e_1_2_1_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(93)90499-G"},{"key":"e_1_2_1_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90379-4"},{"key":"e_1_2_1_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/370183a0"},{"key":"e_1_2_1_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(91)90028-W"},{"key":"e_1_2_1_26_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.90.3.1112"},{"key":"e_1_2_1_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/369669a0"},{"key":"e_1_2_1_28_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1432-1033.1994.00771.x"},{"key":"e_1_2_1_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/363595a0"},{"key":"e_1_2_1_30_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1993.1248"},{"key":"e_1_2_1_31_2","first-page":"73","article-title":"\u201cPHASES\u201d\u2014A program package for the processing and analysis of diffraction data from macromolecules","volume":"18","author":"Furey W.","year":"1990","journal-title":"PA33. 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