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| Content Provider | PubMed Central |
|---|---|
| Author | Ahmad, Shandar Keskin, Ozlem Sarai, Akinori Nussinov, Ruth |
| Copyright Year | 2008 |
| Abstract | Amino acid residues, which play important roles in protein function, are often conserved. Here, we analyze thermodynamic and structural data of protein–DNA interactions to explore a relationship between free energy, sequence conservation and structural cooperativity. We observe that the most stabilizing residues or putative hotspots are those which occur as clusters of conserved residues. The higher packing density of the clusters and available experimental thermodynamic data of mutations suggest cooperativity between conserved residues in the clusters. Conserved singlets contribute to the stability of protein–DNA complexes to a lesser extent. We also analyze structural features of conserved residues and their clusters and examine their role in identifying DNA-binding sites. We show that about half of the observed conserved residue clusters are in the interface with the DNA, which could be identified from their amino acid composition; whereas the remaining clusters are at the protein–protein or protein–ligand interface, or embedded in the structural scaffolds. In protein–protein interfaces, conserved residues are highly correlated with experimental residue hotspots, contributing dominantly and often cooperatively to the stability of protein–protein complexes. Overall, the conservation patterns of the stabilizing residues in DNA-binding proteins also highlight the significance of clustering as compared to single residue conservation. |
| Related Links | http://dx.doi.org/10.1093/nar/gkn573 |
| Ending Page | 5932 |
| Page Count | 11 |
| Starting Page | 5922 |
| File Format | |
| ISSN | 03051048 |
| e-ISSN | 13624962 |
| Journal | Nucleic Acids Research |
| Issue Number | 18 |
| Volume Number | 36 |
| Language | English |
| Publisher | Oxford University Press |
| Publisher Date | 2008-09-01 |
| Access Restriction | Open |
| Rights Holder | Oxford University Press |
| Subject Keyword | Genetics Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Genetics |
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