STRUCTURAL BASIS FOR CHROMOSOME X-LINKED AGAMMAGLOBULINEMIA - A TYROSINE KINASE DISEASE

Forskningsoutput: TidskriftsbidragArtikel 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
  • Mauno Vihinen
  • D VETRIE
  • HS MANIAR
  • HD OCHS
  • QL ZHU
  • I VORECHOVSKY
  • ADB WEBSTER
  • LD NOTARANGELO
  • L NILSSON
  • JM SOWADSKI
  • CIE SMITH
Externa organisationer
  • External Organization - Unknown
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Medicinsk genetik

Nyckelord

Originalspråkengelska
Sidor (från-till)12803-12807
TidskriftProceedings of the National Academy of Sciences
Volym91
Utgivningsnummer26
StatusPublished - 1994
PublikationskategoriForskning
Peer review utfördJa
Externt publiceradJa