Sequence variation in ligand binding sites in proteins
<p>Abstract</p> <p>Background</p> <p>The recent explosion in the availability of complete genome sequences has led to the cataloging of tens of thousands of new proteins and putative proteins. Many of these proteins can be structurally or functionally categorized from s...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
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BMC
2005-09-01
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| Series: | BMC Bioinformatics |
| Online Access: | http://www.biomedcentral.com/1471-2105/6/240 |
| _version_ | 1818515648164134912 |
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| author | Magliery Thomas J Regan Lynne |
| author_facet | Magliery Thomas J Regan Lynne |
| author_sort | Magliery Thomas J |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>The recent explosion in the availability of complete genome sequences has led to the cataloging of tens of thousands of new proteins and putative proteins. Many of these proteins can be structurally or functionally categorized from sequence conservation alone. In contrast, little attention has been given to the meaning of poorly-conserved sites in families of proteins, which are typically assumed to be of little structural or functional importance.</p> <p>Results</p> <p>Recently, using statistical free energy analysis of tetratricopeptide repeat (TPR) domains, we observed that positions in contact with peptide ligands are more variable than surface positions in general. Here we show that statistical analysis of TPRs, ankyrin repeats, Cys<sub>2</sub>His<sub>2 </sub>zinc fingers and PDZ domains accurately identifies specificity-determining positions by their sequence variation. Sequence variation is measured as deviation from a neutral reference state, and we present probabilistic and information theory formalisms that improve upon recently suggested methods such as statistical free energies and sequence entropies.</p> <p>Conclusion</p> <p>Sequence variation has been used to identify functionally-important residues in four selected protein families. With TPRs and ankyrin repeats, protein families that bind highly diverse ligands, the effect is so pronounced that sequence "hypervariation" alone can be used to predict ligand binding sites.</p> |
| first_indexed | 2024-12-11T00:31:32Z |
| format | Article |
| id | doaj.art-817b7a094609442b82b7e34683453a7c |
| institution | Directory Open Access Journal |
| issn | 1471-2105 |
| language | English |
| last_indexed | 2024-12-11T00:31:32Z |
| publishDate | 2005-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Bioinformatics |
| spelling | doaj.art-817b7a094609442b82b7e34683453a7c2022-12-22T01:27:20ZengBMCBMC Bioinformatics1471-21052005-09-016124010.1186/1471-2105-6-240Sequence variation in ligand binding sites in proteinsMagliery Thomas JRegan Lynne<p>Abstract</p> <p>Background</p> <p>The recent explosion in the availability of complete genome sequences has led to the cataloging of tens of thousands of new proteins and putative proteins. Many of these proteins can be structurally or functionally categorized from sequence conservation alone. In contrast, little attention has been given to the meaning of poorly-conserved sites in families of proteins, which are typically assumed to be of little structural or functional importance.</p> <p>Results</p> <p>Recently, using statistical free energy analysis of tetratricopeptide repeat (TPR) domains, we observed that positions in contact with peptide ligands are more variable than surface positions in general. Here we show that statistical analysis of TPRs, ankyrin repeats, Cys<sub>2</sub>His<sub>2 </sub>zinc fingers and PDZ domains accurately identifies specificity-determining positions by their sequence variation. Sequence variation is measured as deviation from a neutral reference state, and we present probabilistic and information theory formalisms that improve upon recently suggested methods such as statistical free energies and sequence entropies.</p> <p>Conclusion</p> <p>Sequence variation has been used to identify functionally-important residues in four selected protein families. With TPRs and ankyrin repeats, protein families that bind highly diverse ligands, the effect is so pronounced that sequence "hypervariation" alone can be used to predict ligand binding sites.</p>http://www.biomedcentral.com/1471-2105/6/240 |
| spellingShingle | Magliery Thomas J Regan Lynne Sequence variation in ligand binding sites in proteins BMC Bioinformatics |
| title | Sequence variation in ligand binding sites in proteins |
| title_full | Sequence variation in ligand binding sites in proteins |
| title_fullStr | Sequence variation in ligand binding sites in proteins |
| title_full_unstemmed | Sequence variation in ligand binding sites in proteins |
| title_short | Sequence variation in ligand binding sites in proteins |
| title_sort | sequence variation in ligand binding sites in proteins |
| url | http://www.biomedcentral.com/1471-2105/6/240 |
| work_keys_str_mv | AT maglierythomasj sequencevariationinligandbindingsitesinproteins AT reganlynne sequencevariationinligandbindingsitesinproteins |