Vihinen, M., Vetrie, D. , Maniar, H. S., Ochs, H. D., Zhu, Q., Vorechovský, I., Webster, A. D. B., Notarangelo, L. D., Nilsson, L. and Sowadski, J. M. (1994) Structural basis for chromosome X-linked agammaglobulinemia: a tyrosine kinase disease. Proceedings of the National Academy of Sciences of the United States of America, 91(26), pp. 12803-12807. (PMID:7809124) (PMCID:PMC45528)
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Abstract
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-->Gln was studied and found to abrogate the tyrosine kinase activity of BTK. All of the eight mutations (Lys-430-->Glu, Arg-520-->Glu, Arg-525-->Gln, Arg-562-->Pro, Ala-582-->Val, Glu-589-->Gly, Gly-594-->Glu, and Gly-613-->Asp) were located on one face of the BTK kinase domain, indicating structural clustering of functionally important residues.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Vetrie, Professor David |
Authors: | Vihinen, M., Vetrie, D., Maniar, H. S., Ochs, H. D., Zhu, Q., Vorechovský, I., Webster, A. D. B., Notarangelo, L. D., Nilsson, L., and Sowadski, J. M. |
College/School: | College of Medical Veterinary and Life Sciences > School of Cancer Sciences |
Journal Name: | Proceedings of the National Academy of Sciences of the United States of America |
Publisher: | National Academy of Sciences |
ISSN: | 0027-8424 |
ISSN (Online): | 1091-6490 |
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