Skip Navigation


PEDS Advance Access originally published online on April 13, 2004
Protein Engineering Design and Selection 2004 17(3):267-276; doi:10.1093/protein/gzh030
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow All Versions of this Article:
17/3/267    most recent
gzh030v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (8)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Shen, B.
Right arrow Articles by Vihinen, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shen, B.
Right arrow Articles by Vihinen, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2004 Oxford University Press

Conservation and covariance in PH domain sequences: physicochemical profile and information theoretical analysis of XLA-causing mutations in the Btk PH domain

Bairong Shen1 and Mauno Vihinen1,2,3

1Institute of Medical Technology, FI-33014 University of Tampere and 2Research Unit, Tampere University Hospital, FI-33520 Tampere, Finland

3 To whom correspondence should be addressed, at the first address. e-mail: mauno.vihinen{at}uta.fi

Mutations that cause X-linked agammaglobulinemia (XLA) appear throughout the Bruton tyrosine kinase (Btk) sequence, including the pleckstrin homology (PH) domain. To analyze the basis of this disease with respect to protein structure, we studied the relationships between PH domain sequences and structures by comparing sequence-based profiles of physicochemical properties and solvent accessibility profiles. The diversity of the distribution of amino acids was measured by calculating entropies for sequences containing mutations at different positions in multiple sequence alignments. Mutual information was calculated to quantify positional covariation. Eight conserved extrema were apparent in all profiles. The majority of the XLA disease-causing mutations in the Btk PH domain were found at positions having significant mutual information, indicating that there are covariant constraints for both structure and function. Together with additional structural analyses, all the XLA mutations that were analyzed could be explained at the molecular level. The method developed here is applicable to the design of mutations for protein engineering.

Received December 29, 2003; revised March 2, 2004; accepted March 18, 2004 Edited by Jane Clarke


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Protein Eng Des SelHome page
B. Shen, J. Bai, and M. Vihinen
Physicochemical feature-based classification of amino acid mutations
Protein Eng. Des. Sel., January 1, 2008; 21(1): 37 - 44.
[Abstract] [Full Text] [PDF]

Home page
 Protein Eng Des SelHome page
J. Thusberg and M. Vihinen
The structural basis of hyper IgM deficiency - CD40L mutations
Protein Eng. Des. Sel., March 1, 2007; 20(3): 133 - 141.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.