STRUCTURAL BASIS FOR CHROMOSOME X-LINKED AGAMMAGLOBULINEMIA - A TYROSINE KINASE DISEASE
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3853307
- author
- publishing date
- 1994
- type
- Contribution to journal
- 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 Academy of 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
- 2016-04-01 12:05:39
- date last changed
- 2021-09-19 03:04:48
@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}}, keywords = {{BRUTON TYROSINE KINASE; BTK; CYTOPLASMIC TYROSINE KINASE; SIGNAL; TRANSDUCTION}}, language = {{eng}}, number = {{26}}, pages = {{12803--12807}}, publisher = {{National Academy of 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}}, doi = {{10.1073/pnas.91.26.12803}}, volume = {{91}}, year = {{1994}}, }