A 'structural' water molecule in the family of fatty acid binding proteins
| Autor: | Franklyn G. Prendergast, Slobodan Macura, Nenad Juranić, Vladimir A Likic |
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| Rok vydání: | 2008 |
| Předmět: |
Models
Molecular Magnetic Resonance Spectroscopy chemistry.chemical_element Nerve Tissue Proteins Crystal structure Crystallography X-Ray Fatty Acid-Binding Proteins Myelin P2 Protein Biochemistry Oxygen Fatty acid-binding protein Molecular dynamics Animals Molecule Peptide bond Binding site Molecular Biology Binding Sites Chemistry Hydrogen bond Fatty Acids Water Hydrogen Bonding Neoplasm Proteins Rats Crystallography Carrier Proteins Fatty Acid-Binding Protein 7 Research Article |
| Zdroj: | Protein Science. 9:497-504 |
| ISSN: | 0961-8368 |
| DOI: | 10.1110/ps.9.3.497 |
| Popis: | A single water molecule (w135), buried within the structure of rat intestinal fatty acid binding protein (I-FABP), is investigated by NMR, molecular dynamics simulations, and analysis of known crystal structures. An ordered water molecule was found in structurally analogous position in 24 crystal structures of nine different members of the family of fatty acid binding proteins. There is a remarkable conservation of the local structure near the w135 binding site among different proteins from this family. NMR cross-relaxation measurements imply that w135 is present in the I-FABP:ANS (1-sulfonato-8-(1')anilinonaphthalene) complex in solution with the residence time of >300 ps. Mean-square positional fluctuations of w135 oxygen observed in MD simulations (0.18 and 0.13 A2) are comparable in magnitude to fluctuations exhibited by the backbone atoms and result from highly constrained binding pocket as revealed by Voronoi volumes (averages of 27.0 +/- 1.8 A3 and 24.7 +/- 2.2 A3 for the two simulations). Escape of w135 from its binding pocket was observed only in one MD simulation. The escape process was initiated by interactions with external water molecules and was accompanied by large deformations in beta-strands D and E. Immediately before the release, w135 assumed three distinct states that differ in hydrogen bonding topology and persisted for about 15 ps each. Computer simulations suggest that escape of w135 from the I-FABP matrix is primarily determined by conformational fluctuations of the protein backbone and interactions with external water molecules. |
| Databáze: | OpenAIRE |
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