An integrated approach to the interpretation of Single Amino Acid Polymorphisms within the framework of CATH and Gene3D
Author(s)
Type
Journal Article
Abstract
Background: The phenotypic effects of sequence variations in protein-coding regions come about
primarily via their effects on the resulting structures, for example by disrupting active sites or affecting
structural stability. In order better to understand the mechanisms behind known mutant phenotypes, and
predict the effects of novel variations, biologists need tools to gauge the impacts of DNA mutations in terms
of their structural manifestation. Although many mutations occur within domains whose structure has been
solved, many more occur within genes whose protein products have not been structurally characterized.
Results: Here we present 3DSim (3D Structural Implication of Mutations), a database and web application
facilitating the localization and visualization of single amino acid polymorphisms (SAAPs) mapped to protein
structures even where the structure of the protein of interest is unknown. The server displays information
on 6514 point mutations, 4865 of them known to be associated with disease. These polymorphisms are
drawn from SAAPdb, which aggregates data from various sources including dbSNP and several pathogenic
mutation databases. While the SAAPdb interface displays mutations on known structures, 3DSim projects
mutations onto known sequence domains in Gene3D. This resource contains sequences annotated with
domains predicted to belong to structural families in the CATH database. Mappings between domain
sequences in Gene3D and known structures in CATH are obtained using a MUSCLE alignment. 1210 threedimensional
structures corresponding to CATH structural domains are currently included in 3DSim; these
domains are distributed across 396 CATH superfamilies, and provide a comprehensive overview of the
distribution of mutations in structural space.
Conclusion: The server is publicly available at http://3DSim.bioinfo.cnio.es/. In addition, the database
containing the mapping between SAAPdb, Gene3D and CATH is available on request and most of the
functionality is available through programmatic web service access.
primarily via their effects on the resulting structures, for example by disrupting active sites or affecting
structural stability. In order better to understand the mechanisms behind known mutant phenotypes, and
predict the effects of novel variations, biologists need tools to gauge the impacts of DNA mutations in terms
of their structural manifestation. Although many mutations occur within domains whose structure has been
solved, many more occur within genes whose protein products have not been structurally characterized.
Results: Here we present 3DSim (3D Structural Implication of Mutations), a database and web application
facilitating the localization and visualization of single amino acid polymorphisms (SAAPs) mapped to protein
structures even where the structure of the protein of interest is unknown. The server displays information
on 6514 point mutations, 4865 of them known to be associated with disease. These polymorphisms are
drawn from SAAPdb, which aggregates data from various sources including dbSNP and several pathogenic
mutation databases. While the SAAPdb interface displays mutations on known structures, 3DSim projects
mutations onto known sequence domains in Gene3D. This resource contains sequences annotated with
domains predicted to belong to structural families in the CATH database. Mappings between domain
sequences in Gene3D and known structures in CATH are obtained using a MUSCLE alignment. 1210 threedimensional
structures corresponding to CATH structural domains are currently included in 3DSim; these
domains are distributed across 396 CATH superfamilies, and provide a comprehensive overview of the
distribution of mutations in structural space.
Conclusion: The server is publicly available at http://3DSim.bioinfo.cnio.es/. In addition, the database
containing the mapping between SAAPdb, Gene3D and CATH is available on request and most of the
functionality is available through programmatic web service access.
Date Issued
2009-08-27
Date Acceptance
2008-09-22
Citation
BMC Bioinformatics, 2009, 10 (Suppl 8)
ISSN
1471-2105
Publisher
BioMed Central
Journal / Book Title
BMC Bioinformatics
Volume
10
Issue
Suppl 8
Copyright Statement
© 2009 Izarzugaza et al; licensee BioMed Central Ltd.
This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0),
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
License URL
Publication Status
Published
Article Number
S5