A 'structural' water molecule in the family of fatty acid binding proteins

Vladimir A. Likić, Nenad Juranić, Slobodan I Macura, Franklyn G. Prendergast

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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 w 135 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 Å2) 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 Å3 and 24.7 ± 2.2 Å3 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 β-strands D and E. Immediately before the release, w 135 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.

Original languageEnglish (US)
Pages (from-to)497-504
Number of pages8
JournalProtein Science
Volume9
Issue number3
StatePublished - 2000

Fingerprint

Fatty Acid-Binding Proteins
Molecules
N-phenyl-1-naphthylamine
Water
Crystal structure
Nuclear magnetic resonance
Computer simulation
Molecular Dynamics Simulation
Hydrogen Bonding
Computer Simulation
Dynamic analysis
Molecular dynamics
Rats
Conservation
Hydrogen bonds
Proteins
Binding Sites
Topology
Oxygen
Atoms

Keywords

  • Buried water
  • I-FABP
  • MD simulations
  • NMR

ASJC Scopus subject areas

  • Biochemistry

Cite this

Likić, V. A., Juranić, N., Macura, S. I., & Prendergast, F. G. (2000). A 'structural' water molecule in the family of fatty acid binding proteins. Protein Science, 9(3), 497-504.

A 'structural' water molecule in the family of fatty acid binding proteins. / Likić, Vladimir A.; Juranić, Nenad; Macura, Slobodan I; Prendergast, Franklyn G.

In: Protein Science, Vol. 9, No. 3, 2000, p. 497-504.

Research output: Contribution to journalArticle

Likić, VA, Juranić, N, Macura, SI & Prendergast, FG 2000, 'A 'structural' water molecule in the family of fatty acid binding proteins', Protein Science, vol. 9, no. 3, pp. 497-504.
Likić, Vladimir A. ; Juranić, Nenad ; Macura, Slobodan I ; Prendergast, Franklyn G. / A 'structural' water molecule in the family of fatty acid binding proteins. In: Protein Science. 2000 ; Vol. 9, No. 3. pp. 497-504.
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