STRUCTURAL BASIS FOR X-LINKED AGAMMAGLOBULINEMIA (XLA) - MUTATIONS AT INTERACTING BTK RESIDUES R562, W563, AND A582
MANIAR, HS ; Vihinen, Mauno LU
; WEBSTER, ADB
; NILSSON, L
and SMITH, CIE
(1995)
In Clinical Immunology and Immunopathology
76(3).
p.198-202
- Abstract
- It has been suggested that tryptophan 563 is sandwiched between residues R562 and A532 in Bruton's agammaglobulinemia tyrosine kinase (Btk). Mutations of the surrounding residues have been shown to cause X-linked agammaglobulinemia. Substitutions R562P and A582V were noticed to have impaired kinase activity. However, based on Western blot analysis, the mutant proteins were expressed at normal levels. Molecular modeling of the kinase domain has previously indicated that these residues presumably govern the position of the W563 side chain, which is thought to interact with the catalytic loop. W563 is inside the molecule and too far away from the catalytic center to interact directly with the substrate or cofactors. To prove these model-based... (More)
- It has been suggested that tryptophan 563 is sandwiched between residues R562 and A532 in Bruton's agammaglobulinemia tyrosine kinase (Btk). Mutations of the surrounding residues have been shown to cause X-linked agammaglobulinemia. Substitutions R562P and A582V were noticed to have impaired kinase activity. However, based on Western blot analysis, the mutant proteins were expressed at normal levels. Molecular modeling of the kinase domain has previously indicated that these residues presumably govern the position of the W563 side chain, which is thought to interact with the catalytic loop. W563 is inside the molecule and too far away from the catalytic center to interact directly with the substrate or cofactors. To prove these model-based conclusions, a conservative substitution with phenylalanine for W563 was made, and the resultant mutant lacked kinase activity. These results confirm our previous assumption that the side chain of W563, invariant in protein tyrosine kinases, is crucial for Btk kinase activity. Mutations in the surrounding residues seem to inactivate Btk by affecting the location of W563. (C) 1996 Academic Press, Inc. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3853178
- author
- MANIAR, HS
; Vihinen, Mauno
LU
; WEBSTER, ADB
; NILSSON, L
and SMITH, CIE
- publishing date
- 1995
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Clinical Immunology and Immunopathology
- volume
- 76
- issue
- 3
- pages
- 198 - 202
- publisher
- Elsevier
- external identifiers
-
- wos:A1995RV96000013
- scopus:0029153304
- ISSN
- 1090-2341
- DOI
- 10.1016/S0090-1229(95)90216-3
- language
- English
- LU publication?
- no
- id
- f99aaa99-0083-4fd0-acad-1c035bd066a7 (old id 3853178)
- date added to LUP
- 2016-04-01 12:18:18
- date last changed
- 2021-01-03 03:51:04
@article{f99aaa99-0083-4fd0-acad-1c035bd066a7,
abstract = {{It has been suggested that tryptophan 563 is sandwiched between residues R562 and A532 in Bruton's agammaglobulinemia tyrosine kinase (Btk). Mutations of the surrounding residues have been shown to cause X-linked agammaglobulinemia. Substitutions R562P and A582V were noticed to have impaired kinase activity. However, based on Western blot analysis, the mutant proteins were expressed at normal levels. Molecular modeling of the kinase domain has previously indicated that these residues presumably govern the position of the W563 side chain, which is thought to interact with the catalytic loop. W563 is inside the molecule and too far away from the catalytic center to interact directly with the substrate or cofactors. To prove these model-based conclusions, a conservative substitution with phenylalanine for W563 was made, and the resultant mutant lacked kinase activity. These results confirm our previous assumption that the side chain of W563, invariant in protein tyrosine kinases, is crucial for Btk kinase activity. Mutations in the surrounding residues seem to inactivate Btk by affecting the location of W563. (C) 1996 Academic Press, Inc.}},
author = {{MANIAR, HS and Vihinen, Mauno and WEBSTER, ADB and NILSSON, L and SMITH, CIE}},
issn = {{1090-2341}},
language = {{eng}},
number = {{3}},
pages = {{198--202}},
publisher = {{Elsevier}},
series = {{Clinical Immunology and Immunopathology}},
title = {{STRUCTURAL BASIS FOR X-LINKED AGAMMAGLOBULINEMIA (XLA) - MUTATIONS AT INTERACTING BTK RESIDUES R562, W563, AND A582}},
url = {{http://dx.doi.org/10.1016/S0090-1229(95)90216-3}},
doi = {{10.1016/S0090-1229(95)90216-3}},
volume = {{76}},
year = {{1995}},
}