{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T14:25:38Z","timestamp":1781101538599,"version":"3.54.1"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"26","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1994,12,20]]},"abstract":"<jats:p>X-linked agammaglobulinemia (XLA) is a hereditary defect of B-cell differentiation in man caused by deficiency of Bruton tyrosine kinase (BTK). A three-dimensional model for the BTK kinase domain, based on the core structure of cAMP-dependent protein kinase, was used to interpret the structural basis for disease in eight independent point mutations in patients with XLA. As Arg-525 of BTK has been thought to functionally substitute for a critical lysine residue in protein-serine kinases, the mutation Arg-525--&gt;Gln was studied and found to abrogate the tyrosine kinase activity of BTK. All of the eight mutations (Lys-430--&gt;Glu, Arg-520--&gt;Glu, Arg-525--&gt;Gln, Arg-562--&gt;Pro, Ala-582--&gt;Val, Glu-589--&gt;Gly, Gly-594--&gt;Glu, and Gly-613--&gt;Asp) were located on one face of the BTK kinase domain, indicating structural clustering of functionally important residues.<\/jats:p>","DOI":"10.1073\/pnas.91.26.12803","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T09:02:49Z","timestamp":1149066169000},"page":"12803-12807","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":59,"title":["Structural basis for chromosome X-linked agammaglobulinemia: a tyrosine kinase disease."],"prefix":"10.1073","volume":"91","author":[{"given":"M","family":"Vihinen","sequence":"first","affiliation":[{"name":"Center for Structural Biochemistry, Karolinska Institute, NOVUM, Huddinge, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Vetrie","sequence":"additional","affiliation":[{"name":"Center for Structural Biochemistry, Karolinska Institute, NOVUM, Huddinge, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H S","family":"Maniar","sequence":"additional","affiliation":[{"name":"Center for Structural Biochemistry, Karolinska Institute, NOVUM, Huddinge, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H D","family":"Ochs","sequence":"additional","affiliation":[{"name":"Center for Structural Biochemistry, Karolinska Institute, NOVUM, Huddinge, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Q","family":"Zhu","sequence":"additional","affiliation":[{"name":"Center for Structural Biochemistry, Karolinska Institute, NOVUM, Huddinge, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Vorechovsk\u00fd","sequence":"additional","affiliation":[{"name":"Center for Structural Biochemistry, Karolinska Institute, NOVUM, Huddinge, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A D","family":"Webster","sequence":"additional","affiliation":[{"name":"Center for Structural Biochemistry, Karolinska Institute, NOVUM, Huddinge, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L D","family":"Notarangelo","sequence":"additional","affiliation":[{"name":"Center for Structural Biochemistry, Karolinska Institute, NOVUM, Huddinge, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L","family":"Nilsson","sequence":"additional","affiliation":[{"name":"Center for Structural Biochemistry, Karolinska Institute, NOVUM, Huddinge, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J M","family":"Sowadski","sequence":"additional","affiliation":[{"name":"Center for Structural Biochemistry, Karolinska Institute, NOVUM, Huddinge, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1994,12,20]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.91.26.12803","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T14:13:02Z","timestamp":1649859182000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.91.26.12803"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1994,12,20]]},"references-count":0,"journal-issue":{"issue":"26","published-print":{"date-parts":[[1994,12,20]]}},"alternative-id":["10.1073\/pnas.91.26.12803"],"URL":"https:\/\/doi.org\/10.1073\/pnas.91.26.12803","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1994,12,20]]},"assertion":[{"value":"1994-12-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}