The solution structure of bovine pancreatic trypsin inhibitor at high pressure

• Published in: Protein science Vol. 12; no. 9; pp. 1971 - 1979
• Main Authors: Williamson, Michael P., Akasaka, Kazuyuki, Refaee, Mohamed
• Format: Journal Article
• Language: English
• Published: Bristol Cold Spring Harbor Laboratory Press 01.09.2003
• Subjects: active site; Animals; Aprotinin - chemistry; Binding Sites; buried water; Cattle; chemical shifts; Cysteine - chemistry; Hydrogen Bonding; Magnetic Resonance Spectroscopy; Models, Molecular; NMR; Phenylalanine - chemistry; Pressure; protein compression; Protein Conformation; Water - chemistry
• ISSN: 0961-8368; 1469-896X
• DOI: 10.1110/ps.0242103

The solution structure of bovine pancreatic trypsin inhibitor (BPTI) at a pressure of 2 kbar is presented. The structure was calculated as a change from an energy‐minimized low‐pressure structure, using 1H chemical shifts as restraints. The structure has changed by 0.24 Å RMS, and has almost unchanged volume. The largest changes as a result of pressure are in the loop 10–16, which contains the active site of BPTI, and residues 38–42, which are adjacent to buried water molecules. Hydrogen bonds are compressed by 0.029 ± 0.117 Å, with the longer hydrogen bonds, including those to internal buried water molecules, being compressed more. The hydrophobic core is also compressed, largely from reduction of packing defects. The parts of the structure that have the greatest change are close to buried water molecules, thus highlighting the importance of water molecules as the nucleation sites for volume fluctuation of proteins in native conditions.