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. 2007 Jul;35(Web Server issue):W384-92.
doi: 10.1093/nar/gkm232. Epub 2007 May 30.

Structure SNP (StSNP): a web server for mapping and modeling nsSNPs on protein structures with linkage to metabolic pathways

Affiliations

Structure SNP (StSNP): a web server for mapping and modeling nsSNPs on protein structures with linkage to metabolic pathways

Alper Uzun et al. Nucleic Acids Res. 2007 Jul.

Abstract

SNPs located within the open reading frame of a gene that result in an alteration in the amino acid sequence of the encoded protein [nonsynonymous SNPs (nsSNPs)] might directly or indirectly affect functionality of the protein, alone or in the interactions in a multi-protein complex, by increasing/decreasing the activity of the metabolic pathway. Understanding the functional consequences of such changes and drawing conclusions about the molecular basis of diseases, involves integrating information from multiple heterogeneous sources including sequence, structure data and pathway relations between proteins. The data from NCBI's SNP database (dbSNP), gene and protein databases from Entrez, protein structures from the PDB and pathway information from KEGG have all been cross referenced into the StSNP web server, in an effort to provide combined integrated, reports about nsSNPs. StSNP provides 'on the fly' comparative modeling of nsSNPs with links to metabolic pathway information, along with real-time visual comparative analysis of the modeled structures using the Friend software application. The use of metabolic pathways in StSNP allows a researcher to examine possible disease-related pathways associated with a particular nsSNP(s), and link the diseases with the current available molecular structure data. The server is publicly available at http://glinka.bio.neu.edu/StSNP/.

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Figures

Figure 1.
Figure 1.
StSNP is an interactive web server, which utilizes several heterogeneous data sources.
Figure 2.
Figure 2.
Data generation in StSNP. (A) Main query page, (B) Formatted data for nsSNPs along with graphical alignment representation, (C) nsSNP(s) selection for modeling, (D) Output page, and (E) Visualization in the Friend applet.
Figure 3.
Figure 3.
(A) Glutathione S Transferase is shown with nsSNP locations displayed in ball and stick representation, with I105V marked with a black circle. The reference residues are shown in blue, nonsynonymous residues in red and the substrate glutathione is displayed in space fill representation (yellow). The query for the example was Protein ID NP_000843 and template PDB ID 1aqv chain B. (B) The Results section also provides a user with a link to glutathione metabolism in order to view other members found in the pathway.
Figure 4.
Figure 4.
Aldehyde dehydrogenase-2 is shown with nsSNP locations displayed in ball and stick representation, with E504K marked with a black circle. The reference residues are shown in blue, nonsynonymous residues in red and the substrate NAD is displayed in space fill representation (green). The query for the example was Protein ID NP_000681 and template PDB ID 1ag8 chain A.

References

    1. Consortium. The International HapMap Project. Nature. 2003;426:789–796. - PubMed
    1. Sachidanandam R, Weissman D, Schmidt SC, Kakol JM, Stein LD, Marth G, Sherry S, Mullikin JC, Mortimore BJ, et al. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature. 2001;409:928–933. - PubMed
    1. Sherry ST, Ward M, Sirotkin K. dbSNP-database for single nucleotide polymorphisms and other classes of minor genetic variation. Genome Res. 1999;9:677–679. - PubMed
    1. Chasman D, Adams RM. Predicting the functional consequences of non-synonymous single nucleotide polymorphisms: structure-based assessment of amino acid variation. J. Mol. Biol. 2001;307:683–706. - PubMed
    1. Fredman D, Siegfried M, Yuan YP, Bork P, Lehvaslaiho H, Brookes AJ. HGVbase: a human sequence variation database emphasizing data quality and a broad spectrum of data sources. Nucleic Acids Res. 2002;30:387–391. - PMC - PubMed