Demonstration of Positionally Disordered Water Within a Protein Hydrophobic Cavity by NMR

• Published in: Science (American Association for the Advancement of Science) Vol. 267; no. 5205; pp. 1813 - 1817
• Main Authors: Ernst, James A., Clubb, Robert T., Zhou, Huan-Xiang, Gronenborn, Angela M., Clore, G. Marius
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 24-03-1995; American Association for the Advancement of Science
• Subjects: Atoms; Biological and medical sciences; Conformational dynamics in molecular biology; Crystal structure; Electrical potential; Electrochemistry; Electrostatics; Fundamental and applied biological sciences. Psychology; Humans; Hydration; Hydrogen Bonding; Interleukin-1 - chemistry; Magnetic Resonance Spectroscopy; Models, Chemical; Models, Molecular; Molecular biophysics; Molecules; Nuclear magnetic resonance; Nuclear magnetic resonance spectroscopy; Protein Conformation; Proteins; Protons; Rehydration solutions; Solvents; Surface water; Water - analysis; Water - chemistry; Human; Hydration; Cytokine; Molecular interaction; Interleukin 1β; Bound water; Structural analysis; Conformation
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.7892604

The presence and location of water of hydration (that is, bound water) in the solution structure of human interleukin-1β (hlL-1β) was investigated with water-selective two-dimensional heteronuclear magnetic resonance spectroscopy. It is shown here that in addition to water at the surface of the protein and ordered internal water molecules involved in bridging hydrogen bonds, positionally disordered water is present within a large, naturally occurring hydrophobic cavity located at the center of the molecule. These water molecules of hydration have residency times in the range of 1 to 2 nanoseconds to 100 to 200 microseconds and can be readily detected by nuclear magnetic resonance (NMR). Thus, large hydrophobic cavities in proteins may not be truly empty, as analysis of crystal structures appears to show, but may contain mobile water molecules that are crystallographically invisible but detectable by NMR.