Structural basis for chromosome X-linked agammaglobulinemia: a tyrosine kinase disease.

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)

Full text not currently available from Enlighten.

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
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

University Staff: Request a correction | Enlighten Editors: Update this record