STRUCTURAL BASIS FOR CHROMOSOME X-LINKED AGAMMAGLOBULINEMIA - A TYROSINE KINASE DISEASE
Forskningsoutput: Tidskriftsbidrag › Artikel i vetenskaplig tidskrift
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.
Detaljer
Författare | |
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Externa organisationer |
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Forskningsområden | Ämnesklassifikation (UKÄ) – OBLIGATORISK
Nyckelord |
Originalspråk | engelska |
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Sidor (från-till) | 12803-12807 |
Tidskrift | Proceedings of the National Academy of Sciences |
Volym | 91 |
Utgåva nummer | 26 |
Status | Published - 1994 |
Publikationskategori | Forskning |
Peer review utförd | Ja |
Externt publicerad | Ja |