{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T11:39:22Z","timestamp":1778067562183,"version":"3.51.4"},"reference-count":56,"publisher":"Elsevier BV","issue":"12","license":[{"start":{"date-parts":[[2009,12,1]],"date-time":"2009-12-01T00:00:00Z","timestamp":1259625600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2013,8,22]],"date-time":"2013-08-22T00:00:00Z","timestamp":1377129600000},"content-version":"vor","delay-in-days":1360,"URL":"https:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Structure"],"published-print":{"date-parts":[[2009,12]]},"DOI":"10.1016\/j.str.2009.10.011","type":"journal-article","created":{"date-parts":[[2009,12,9]],"date-time":"2009-12-09T12:27:14Z","timestamp":1260361634000},"page":"1669-1678","source":"Crossref","is-referenced-by-count":58,"title":["Structural Basis of the Cofactor- and Substrate-Assisted Activation of Human Coagulation Factor IXa"],"prefix":"10.1016","volume":"17","author":[{"given":"Thomas","family":"Z\u00f6gg","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Brandstetter","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.str.2009.10.011_bib1","doi-asserted-by":"crossref","first-page":"12534","DOI":"10.1021\/bi001477q","article-title":"Preparation, characterization, and the crystal structure of the inhibitor ZK-807834 (CI-1031) complexed with factor Xa","volume":"39","author":"Adler","year":"2000","journal-title":"Biochemistry"},{"key":"10.1016\/j.str.2009.10.011_bib2","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/0003-9861(81)90546-4","article-title":"The interaction of Ca2+ with human Factor IX","volume":"208","author":"Amphlett","year":"1981","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1016\/j.str.2009.10.011_bib3","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1073\/pnas.89.1.152","article-title":"Antibody-probed conformational transitions in the protease domain of human factor IX upon calcium binding and zymogen activation: putative high-affinity Ca(2+)-binding site in the protease domain","volume":"89","author":"Bajaj","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.str.2009.10.011_bib4","doi-asserted-by":"crossref","first-page":"16302","DOI":"10.1074\/jbc.M011680200","article-title":"Factor IXa:factor VIIIa interaction. helix 330-338 of factor ixa interacts with residues 558-565 and spatially adjacent regions of the a2 subunit of factor VIIIa","volume":"276","author":"Bajaj","year":"2001","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.str.2009.10.011_bib5","doi-asserted-by":"crossref","first-page":"3467","DOI":"10.1002\/j.1460-2075.1989.tb08511.x","article-title":"The refined 1.9 A crystal structure of human alpha-thrombin: interaction with D-Phe-Pro-Arg chloromethylketone and significance of the Tyr-Pro-Pro-Trp insertion segment","volume":"8","author":"Bode","year":"1989","journal-title":"EMBO J."},{"key":"10.1016\/j.str.2009.10.011_bib6","doi-asserted-by":"crossref","first-page":"9796","DOI":"10.1073\/pnas.92.21.9796","article-title":"X-ray structure of clotting factor IXa: active site and module structure related to Xase activity and hemophilia B","volume":"92","author":"Brandstetter","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.str.2009.10.011_bib7","doi-asserted-by":"crossref","first-page":"29988","DOI":"10.1074\/jbc.271.47.29988","article-title":"X-ray structure of active site-inhibited clotting factor Xa. Implications for drug design and substrate recognition","volume":"271","author":"Brandstetter","year":"1996","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.str.2009.10.011_bib8","doi-asserted-by":"crossref","first-page":"2728","DOI":"10.1038\/nprot.2007.406","article-title":"Version 1.2 of the crystallography and NMR system","volume":"2","author":"Br\u00fcnger","year":"2007","journal-title":"Nat. Protoc."},{"key":"10.1016\/j.str.2009.10.011_bib9","doi-asserted-by":"crossref","first-page":"5336","DOI":"10.1016\/S0021-9258(19)70791-1","article-title":"A kinetic evaluation of activated bovine blood coagulation factor IX toward synthetic substrates","volume":"255","author":"Byrne","year":"1980","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.str.2009.10.011_bib10","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1021\/bi00274a004","article-title":"Reactivity of bovine blood coagulation factor IXa beta, factor Xa beta, and factor XIa toward fluorogenic peptides containing the activation site sequences of bovine factor IX and factor X","volume":"22","author":"Castillo","year":"1983","journal-title":"Biochemistry"},{"key":"10.1016\/j.str.2009.10.011_bib11","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1107\/S0907444994003112","article-title":"The CCP4 suite: programs for protein crystallography","volume":"50","year":"1994","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"10.1016\/j.str.2009.10.011_bib12","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1021\/bi00299a009","article-title":"Active-site mapping of bovine and human blood coagulation serine proteases using synthetic peptide 4-nitroanilide and thio ester substrates","volume":"23","author":"Cho","year":"1984","journal-title":"Biochemistry"},{"key":"10.1016\/j.str.2009.10.011_bib13","doi-asserted-by":"crossref","first-page":"10653","DOI":"10.1073\/pnas.93.20.10653","article-title":"Residue 225 determines the Na(+)-induced allosteric regulation of catalytic activity in serine proteases","volume":"93","author":"Dang","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.str.2009.10.011_bib14","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1016\/S1359-6446(04)03363-X","article-title":"The case for open-source software in drug discovery","volume":"10","author":"DeLano","year":"2005","journal-title":"Drug Discov. Today"},{"key":"10.1016\/j.str.2009.10.011_bib15","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/S0969-2126(01)00624-4","article-title":"The factor VII zymogen structure reveals reregistration of beta strands during activation","volume":"9","author":"Eigenbrot","year":"2001","journal-title":"Structure"},{"key":"10.1016\/j.str.2009.10.011_bib16","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1182\/blood.V64.4.821.821","article-title":"Cleavage and activation of human factor IX by serine proteases","volume":"64","author":"Enfield","year":"1984","journal-title":"Blood"},{"key":"10.1016\/j.str.2009.10.011_bib17","doi-asserted-by":"crossref","first-page":"19049","DOI":"10.1074\/jbc.273.30.19049","article-title":"The A2 subunit of factor VIIIa modulates the active site of factor IXa","volume":"273","author":"Fay","year":"1998","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.str.2009.10.011_bib18","doi-asserted-by":"crossref","first-page":"4508","DOI":"10.1021\/bi00719a006","article-title":"The mechanism of activation of bovine factor IX (Christmas factor) by bovine factor XIa (activated plasma thromboplastin antecedent)","volume":"13","author":"Fujikawa","year":"1974","journal-title":"Biochemistry"},{"key":"10.1016\/j.str.2009.10.011_bib19","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1073\/pnas.0710894105","article-title":"Structural identification of the pathway of long-range communication in an allosteric enzyme","volume":"105","author":"Gandhi","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.str.2009.10.011_bib20","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1160\/TH06-03-0156","article-title":"The influence of sodium ion binding on factor IXa activity","volume":"95","author":"Gopalakrishna","year":"2006","journal-title":"Thromb. Haemost."},{"key":"10.1016\/j.str.2009.10.011_bib21","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1107\/S0907444900019168","article-title":"Geometry of metal-ligand interactions in proteins","volume":"57","author":"Harding","year":"2001","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"10.1016\/j.str.2009.10.011_bib22","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1107\/S0907444902003712","article-title":"Metal-ligand geometry relevant to proteins and in proteins: sodium and potassium","volume":"58","author":"Harding","year":"2002","journal-title":"Acta Crystallogr. D Biol. Crystallogr."},{"key":"10.1016\/j.str.2009.10.011_bib23","doi-asserted-by":"crossref","first-page":"6626","DOI":"10.1093\/emboj\/16.22.6626","article-title":"Converting blood coagulation factor IXa into factor Xa: dramatic increase in amidolytic activity identifies important active site determinants","volume":"16","author":"Hopfner","year":"1997","journal-title":"EMBO J."},{"key":"10.1016\/j.str.2009.10.011_bib24","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/S0969-2126(99)80125-7","article-title":"Coagulation factor IXa: the relaxed conformation of Tyr99 blocks substrate binding","volume":"7","author":"Hopfner","year":"1999","journal-title":"Structure"},{"key":"10.1016\/j.str.2009.10.011_bib25","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1038\/35038119","article-title":"Structure of a serpin-protease complex shows inhibition by deformation","volume":"407","author":"Huntington","year":"2000","journal-title":"Nature"},{"key":"10.1016\/j.str.2009.10.011_bib26","first-page":"35","article-title":"Interaction of tissue factor and factor VII at the earliest phase of coagulation","volume":"17","author":"Josso","year":"1965","journal-title":"Thromb. Diath. Haemorrh. Suppl."},{"key":"10.1016\/j.str.2009.10.011_bib27","doi-asserted-by":"crossref","first-page":"7398","DOI":"10.1021\/bi992735q","article-title":"Insertion loop 256-268 in coagulation factor IX restricts enzymatic activity in the absence but not in the presence of factor VIII","volume":"39","author":"Kolkman","year":"2000","journal-title":"Biochemistry"},{"key":"10.1016\/j.str.2009.10.011_bib28","doi-asserted-by":"crossref","first-page":"6461","DOI":"10.1073\/pnas.79.21.6461","article-title":"Isolation and characterization of a cDNA coding for human factor IX","volume":"79","author":"Kurachi","year":"1982","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.str.2009.10.011_bib29","doi-asserted-by":"crossref","first-page":"862","DOI":"10.1055\/s-0037-1616144","article-title":"Factor IX Denver, ASN 346\u2192ASP mutation resulting in a dysfunctional protein with defective factor VIIIa interaction","volume":"86","author":"Lefkowitz","year":"2001","journal-title":"Thromb. Haemost."},{"key":"10.1016\/j.str.2009.10.011_bib30","doi-asserted-by":"crossref","first-page":"14884","DOI":"10.1074\/jbc.270.25.14884","article-title":"Cleavage at arginine 145 in human blood coagulation factor IX converts the zymogen into a factor VIII binding enzyme","volume":"270","author":"Lenting","year":"1995","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.str.2009.10.011_bib31","volume":"26","author":"Leslie","year":"1992","journal-title":"Newsl. Protein Crystallogr."},{"key":"10.1016\/j.str.2009.10.011_bib32","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.1016\/S0021-9258(19)62334-3","article-title":"Activation of bovine factor IX (Christmas factor) by factor XIa (activated plasma thromboplastin antecedent) and a protease from Russell's viper venom","volume":"253","author":"Lindquist","year":"1978","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.str.2009.10.011_bib33","doi-asserted-by":"crossref","first-page":"7627","DOI":"10.1021\/bi00398a015","article-title":"Degradation of coagulation proteins by an enzyme from Malayan pit viper (Akistrodon rhodostoma) venom","volume":"26","author":"Lollar","year":"1987","journal-title":"Biochemistry"},{"key":"10.1016\/j.str.2009.10.011_bib34","doi-asserted-by":"crossref","first-page":"23418","DOI":"10.1074\/jbc.272.37.23418","article-title":"Interaction of factor IXa with factor VIIIa. Effects of protease domain Ca2+ binding site, proteolysis in the autolysis loop, phospholipid, and factor X","volume":"272","author":"Mathur","year":"1997","journal-title":"J.\u00a0Biol. Chem."},{"key":"10.1016\/j.str.2009.10.011_bib35","doi-asserted-by":"crossref","first-page":"7196","DOI":"10.1021\/bi00528a022","article-title":"Mapping the active sites of bovine thrombin, factor IXa, factor Xa, factor XIa, factor XIIa, plasma kallikrein, and trypsin with amino acid and peptide thioesters: development of new sensitive substrates","volume":"20","author":"McRae","year":"1981","journal-title":"Biochemistry"},{"key":"10.1016\/j.str.2009.10.011_bib36","doi-asserted-by":"crossref","first-page":"5698","DOI":"10.1016\/S0021-9258(18)91070-7","article-title":"Derivatives of blood coagulation factor IX contain a high affinity Ca2+-binding site that lacks gamma-carboxyglutamic acid","volume":"259","author":"Morita","year":"1984","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.str.2009.10.011_bib37","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1046\/j.1365-2516.2003.00727.x","article-title":"Analysis of haemophilia B database and strategies for identification of common point mutations in the factor IX gene","volume":"9","author":"Mukherjee","year":"2003","journal-title":"Haemophilia"},{"key":"10.1016\/j.str.2009.10.011_bib38","doi-asserted-by":"crossref","first-page":"17012","DOI":"10.1016\/S0021-9258(18)41886-8","article-title":"The active site of factor IXa is located far above the membrane surface and its conformation is altered upon association with factor VIIIa. A fluorescence study","volume":"267","author":"Mutucumarana","year":"1992","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.str.2009.10.011_bib39","doi-asserted-by":"crossref","first-page":"970","DOI":"10.1055\/s-0038-1649709","article-title":"Importance of substrate composition, pH and other variables on tissue factor enhancement of factor VIIa activity","volume":"70","author":"Neuenschwander","year":"1993","journal-title":"Thromb. Haemost."},{"key":"10.1016\/j.str.2009.10.011_bib40","doi-asserted-by":"crossref","first-page":"5260","DOI":"10.1073\/pnas.74.12.5260","article-title":"Activation of factor IX by the reaction product of tissue factor and factor VII: additional pathway for initiating blood coagulation","volume":"74","author":"Osterud","year":"1977","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.str.2009.10.011_bib41","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1152\/physrev.00008.2006","article-title":"Role of Na+ and K+ in enzyme function","volume":"86","author":"Page","year":"2006","journal-title":"Physiol. Rev."},{"key":"10.1016\/j.str.2009.10.011_bib42","doi-asserted-by":"crossref","first-page":"13785","DOI":"10.1073\/pnas.2333109100","article-title":"Redesigning the monovalent cation specificity of an enzyme","volume":"100","author":"Prasad","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"10.1016\/j.str.2009.10.011_bib43","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1007\/s00508-009-1156-0","article-title":"Austrian Hemophilia Registry: design, development and set of variables","volume":"121","author":"Reitter","year":"2009","journal-title":"Wien. Klin. Wochenschr."},{"key":"10.1016\/j.str.2009.10.011_bib44","doi-asserted-by":"crossref","first-page":"8176","DOI":"10.1016\/S0021-9258(18)53078-7","article-title":"Analysis of the functions of the first epidermal growth factor-like domain of factor X","volume":"268","author":"Rezaie","year":"1993","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.str.2009.10.011_bib45","doi-asserted-by":"crossref","first-page":"4400","DOI":"10.1002\/anie.200500883","article-title":"Quantification of cation-pi interactions in protein-ligand complexes: crystal-structure analysis of Factor Xa bound to a quaternary ammonium ion ligand","volume":"44","author":"Sch\u00e4rer","year":"2005","journal-title":"Angew. Chem. Int. Ed. Engl."},{"key":"10.1016\/j.str.2009.10.011_bib46","doi-asserted-by":"crossref","first-page":"28987","DOI":"10.1074\/jbc.M201892200","article-title":"Thermodynamic linkage between the S1 site, the Na+ site, and the Ca2+ site in the protease domain of human activated protein C (APC). Sodium ion in the APC crystal structure is coordinated to four carbonyl groups from two separate loops","volume":"277","author":"Schmidt","year":"2002","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.str.2009.10.011_bib47","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.jmb.2005.04.052","article-title":"Na+ site in blood coagulation factor IXa: effect on catalysis and factor VIIIa binding","volume":"350","author":"Schmidt","year":"2005","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.str.2009.10.011_bib48","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/S0022-2836(02)00747-7","article-title":"Crystal structures of uninhibited factor VIIa link its cofactor and substrate-assisted activation to specific interactions","volume":"322","author":"Sichler","year":"2002","journal-title":"J. Mol. Biol."},{"key":"10.1016\/j.str.2009.10.011_bib49","doi-asserted-by":"crossref","first-page":"4121","DOI":"10.1074\/jbc.M210722200","article-title":"Physiological fIXa activation involves a cooperative conformational rearrangement of the 99-loop","volume":"278","author":"Sichler","year":"2003","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.str.2009.10.011_bib50","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1093\/bioinformatics\/btm622","article-title":"A note on difficult structure alignment problems","volume":"24","author":"Sippl","year":"2008","journal-title":"Bioinformatics"},{"key":"10.1016\/j.str.2009.10.011_bib51","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/S0014-5793(97)00811-9","article-title":"Dramatic enhancement of the catalytic activity of coagulation factor IXa by alcohols","volume":"412","author":"St\u00fcrzebecher","year":"1997","journal-title":"FEBS Lett."},{"key":"10.1016\/j.str.2009.10.011_bib52","unstructured":"Turk, D. (1992). Doctoral Thesis (Technische Universit\u00e4t M\u00fcnchen)."},{"key":"10.1016\/j.str.2009.10.011_bib53","doi-asserted-by":"crossref","first-page":"36876","DOI":"10.1074\/jbc.M001386200","article-title":"Thermodynamic linkage between the S1 site, the Na+ site, and the Ca2+ site in the protease domain of human coagulation factor xa. Studies on catalytic efficiency and inhibitor binding","volume":"275","author":"Underwood","year":"2000","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.str.2009.10.011_bib54","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1107\/S0021889897006766","article-title":"MOLREP: an automated program for molecular replacement","volume":"30","author":"Vagin","year":"1997","journal-title":"J. Appl. Crystallogr."},{"key":"10.1016\/j.str.2009.10.011_bib55","doi-asserted-by":"crossref","first-page":"3433","DOI":"10.1016\/S0021-9258(19)69627-4","article-title":"The role of phospholipid and factor VIIIa in the activation of bovine factor X","volume":"256","author":"van Dieijen","year":"1981","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.str.2009.10.011_bib56","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1515\/BC.2009.057","article-title":"Activation mechanisms of coagulation factor IX","volume":"390","author":"Z\u00f6gg","year":"2009","journal-title":"Biol. Chem."}],"container-title":["Structure"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0969212609004158?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0969212609004158?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2021,10,15]],"date-time":"2021-10-15T20:20:35Z","timestamp":1634329235000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0969212609004158"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,12]]},"references-count":56,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2009,12]]}},"alternative-id":["S0969212609004158"],"URL":"https:\/\/doi.org\/10.1016\/j.str.2009.10.011","relation":{},"ISSN":["0969-2126"],"issn-type":[{"value":"0969-2126","type":"print"}],"subject":[],"published":{"date-parts":[[2009,12]]}}}