Hostname: page-component-cc8bf7c57-fxdwj Total loading time: 0 Render date: 2024-12-11T04:57:00.771Z Has data issue: false hasContentIssue false

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

Published online by Cambridge University Press:  01 March 2000

VLADIMIR A. LIKIĆ
Affiliation:
Department of Pharmacology Research, Mayo Clinic and Foundation, Rochester, Minnesota 55905
NENAD JURANIĆ
Affiliation:
Department of Biochemistry and Molecular Biology, Mayo Clinic and Foundation, Rochester, Minnesota 55905
SLOBODAN MACURA
Affiliation:
Department of Biochemistry and Molecular Biology, Mayo Clinic and Foundation, Rochester, Minnesota 55905
FRANKLYN G. PRENDERGAST
Affiliation:
Department of Pharmacology Research, Mayo Clinic and Foundation, Rochester, Minnesota 55905
Get access

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 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 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, 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.

Type
Research Article
Copyright
© 2000 The Protein Society

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)