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

Vihinen, Mauno LU ; VETRIE, D; MANIAR, HS; OCHS, HD; ZHU, QL; VORECHOVSKY, I; WEBSTER, ADB; NOTARANGELO, LD; NILSSON, L and SOWADSKI, JM, et al. (1994) In Proceedings of the National Academy of Sciences 91(26). p.12803-12807
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,... (More)
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. (Less)
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publication status
published
subject
keywords
BRUTON TYROSINE KINASE, BTK, CYTOPLASMIC TYROSINE KINASE, SIGNAL, TRANSDUCTION
in
Proceedings of the National Academy of Sciences
volume
91
issue
26
pages
12803 - 12807
publisher
National Acad Sciences
external identifiers
  • wos:A1994PY29400093
  • scopus:0028577730
ISSN
1091-6490
DOI
10.1073/pnas.91.26.12803
language
English
LU publication?
no
id
87a72987-2480-472c-97bc-7549d81e6036 (old id 3853307)
date added to LUP
2013-06-28 14:39:17
date last changed
2017-08-06 03:40:54
@article{87a72987-2480-472c-97bc-7549d81e6036,
  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.},
  author       = {Vihinen, Mauno and VETRIE, D and MANIAR, HS and OCHS, HD and ZHU, QL and VORECHOVSKY, I and WEBSTER, ADB and NOTARANGELO, LD and NILSSON, L and SOWADSKI, JM and SMITH, CIE},
  issn         = {1091-6490},
  keyword      = {BRUTON TYROSINE KINASE,BTK,CYTOPLASMIC TYROSINE KINASE,SIGNAL,TRANSDUCTION},
  language     = {eng},
  number       = {26},
  pages        = {12803--12807},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {STRUCTURAL BASIS FOR CHROMOSOME X-LINKED AGAMMAGLOBULINEMIA - A TYROSINE KINASE DISEASE},
  url          = {http://dx.doi.org/10.1073/pnas.91.26.12803},
  volume       = {91},
  year         = {1994},
}