Determination of a high-quality nuclear magnetic resonance solution structure of the bovine pancreatic trypsin inhibitor and comparison with three crystal structures

Berndt, Kurt D.; Güntert, Peter; Orbons, Leonard P. M.; Wüthrich, Kurt

doi:10.1016/0022-2836(92)90222-6

Cited by 194 publications

(171 citation statements)

References 51 publications

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“…19 Figure 2 shows the RMSD of the protein's heavy atoms for the same systems with respect to the crystal structure. The insets in each figure are the RMSD values of 20 different NMR structures 25 compared to the experimental crystal structure. 20 The variations from the crystal structure for all six systems are comparable to the variations seen between the NMR and the crystallographical experiments.…”

Section: Structure Of the Proteinmentioning

confidence: 99%

Structure and Dynamics of the Solvation of Bovine Pancreatic Trypsin Inhibitor in Explicit Water: A Comparative Study of the Effects of Solvent and Protein Polarizability

et al. 2005

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To isolate the effects of the inclusion of polarizability in the force field model on the structure and dynamics of the solvating water in differing electrostatic environments of proteins, we present the results of molecular dynamics simulations of the bovine pancreatic trypsin inhibitor (BPTI) in water with force fields that explicitly include polarization for both the protein and the water. We use three model potentials for water and two model potentials for the protein. Two of the water models and one of the protein models are polarizable. A total of six systems were simulated representing all combinations of these polarizable and nonpolarizable protein and water force fields. We find that all six systems behave in a similar manner in regions of the protein that are weakly electrostatic (either hydrophobic or weakly hydrophilic). However, in the vicinity of regions of the protein with relatively strong electrostatic fields (near positively or negatively charged residues), we observe that the water structure and dynamics are dependent on both the model of the protein and the model of the water. We find that a large part of the dynamical dependence can be described by small changes in the local environments of each region that limit the local density of non-hydrogen-bonded waters, precisely the water molecules that facilitate the dynamical relaxation of the water-water hydrogen bonds. We introduce a simple method for rescaling for this effect. When this is done, we are able to effectively isolate the influence of polarizability on the dynamics. We find that the solvating water's relaxation is most affected when both the protein and the water models are polarizable. However, when only one model (or neither) is polarizable, the relaxation is similar regardless of the models used.

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Section: Structure Of the Proteinmentioning

confidence: 99%

Structure and Dynamics of the Solvation of Bovine Pancreatic Trypsin Inhibitor in Explicit Water: A Comparative Study of the Effects of Solvent and Protein Polarizability

et al. 2005

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“…Figures 9 to 11 show the location and hydrogen bonding of the four internal water molecules of BPTI in crystal form II (Wlodawer et al, 1984). (The solution structure of BPTI is nearly identical to the crystal structure (Berndt et al, 1992).) The hydrogen bond geometries for these internal water molecules are summarized in Table 1.…”

Section: Internal Watermentioning

confidence: 99%

Protein Hydration Dynamics in Aqueous Solution: A Comparison of Bovine Pancreatic Trypsin Inhibitor and Ubiquitin by Oxygen-17 Spin Relaxation Dispersion

Денисов

Halle

1995

Journal of Molecular Biology

162

177

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Water oxygen-17 spin relaxation was used to study hydration and dynamics Condensed Matter Magnetic Resonance Group, Chemical of the globular proteins bovine pancreatic trypsin inhibitor (BPTI) and ubiquitin in aqueous solution. The frequency dispersion of the longitudinal Center, Lund University P. O. Box 124, S-22100 Lund and transverse relaxation rates was measured over the Larmor frequency Sweden range 2.6 to 49 MHz in the pD range 2 to 11 at 27°C. While the protein-induced relaxation enhancement was similar for the two proteins at high frequencies, it was an order of magnitude smaller for ubiquitin than for BPTI at low frequencies. This difference was ascribed to the abscence, in ubiquitin, of highly ordered internal water molecules, which are known to be present in BPTI and in most other globular proteins. These observations demonstrate that the water relaxation dispersion in protein solutions is essentially due to a few structural water molecules buried within the protein matrix, but exchanging rapidly with the external water. The relaxation data indicate that the internal water molecules of BPTI exchange with bulk water on the time-scale 10 −8 to 10 −6 second thus lowering the recently reported upper bound on the residence time of these internal water molecules by four orders of magnitude, and implying that local unfolding occurs on the submicrosecond time-scale. The water molecules residing at the surface of the two proteins were found to be highly mobile, with an average rotational correlation time of approximately 20 picoseconds. For both proteins, the oxygen-17 relaxation depended only very weakly on pD, showing that ionic residues do not perturb hydration water dynamics more than other surface residues. We believe that the present results resolve the long-standing controversy regarding the mechanism behind the spin relaxation dispersion of water nuclei in protein solutions, thus establishing oxygen-17 relaxation as a powerful tool for studies of structurally and functionally important water molecules in proteins and other biomolecules.

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“…The first X-ray structure dates from 1975 (Deisenhofer & Steigemann,1 975)> and two additional crystal forms of the protein followed (Wlodawer et al 1984; and have been compared to the first form (Wlodawer et al 19876). Very recently, a new NMR structure has appeared and it was also compared to all three crystal structures (Berndt et al 1992). Similar tools to the ones used in the present study were applied in this BPTI comparison.…”

Section: Trypsin Inhibitor (Bpti)mentioning

confidence: 99%

Comparison of protein structures determined by NMR in solution and by X-ray diffraction in single crystals

Billeter¹

1992

Quart. Rev. Biophys.

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Following the first determinations of protein structures in the late 1950s and the early 1960s (see for example Kendrewet al.1960; Perutz, 1964), the three-dimensional structures of several hundred proteins have been elucidated by X-ray diffraction on single crystals. By the end of 1991, approximately 150 entries of proteins with substantially different sequences and a well resolved structure (Hobohmet al.1992) were deposited in the Protein Data Bank (Bernsteinet al.1977; Abolaet al.1987). In addition, many structures of homologous proteins or of mutants have been described, bringing the total number of entries to about 600. While it was soon accepted that almost all of these structures do indeed give a correct picture of the fold of the active protein in spite of the non-physiological environment of single crystals, it is not clear to what extent structural details are reliably described by these structures. In particular the surface of a protein may be modified due to the dense packing of protein molecules in the crystal lattice. A detailed knowledge of the protein surface is, however, essential for the understanding of the function of the protein.

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Determination of a high-quality nuclear magnetic resonance solution structure of the bovine pancreatic trypsin inhibitor and comparison with three crystal structures

Cited by 194 publications

References 51 publications

Structure and Dynamics of the Solvation of Bovine Pancreatic Trypsin Inhibitor in Explicit Water: A Comparative Study of the Effects of Solvent and Protein Polarizability

Structure and Dynamics of the Solvation of Bovine Pancreatic Trypsin Inhibitor in Explicit Water: A Comparative Study of the Effects of Solvent and Protein Polarizability

Protein Hydration Dynamics in Aqueous Solution: A Comparison of Bovine Pancreatic Trypsin Inhibitor and Ubiquitin by Oxygen-17 Spin Relaxation Dispersion

Comparison of protein structures determined by NMR in solution and by X-ray diffraction in single crystals

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