Crystallographic refinement of the structure of bovine pancreatic trypsin inhibitor at l.5 Å resolution

Deisenhofer, Johann; Steigemann, W.

doi:10.1107/s0567740875002415

Cited by 582 publications

(291 citation statements)

References 9 publications

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“…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 Proteinsupporting

confidence: 70%

“…Figure 1 shows the root-mean-square deviation (RMSD) of the backbone α-carbons for the three of the simulated systems (OPLS-AA/TIP4P-FQ, PFF/TIP4P, and OPLS-AA/RPOL) with respect to the crystal structure. 20 Results for the other three systems (OPLS-AA/TIP4P, PFF/ TIP4P-FQ, and PFF/RPOL) were presented in a previous work. 19 Figure 2 shows the RMSD of the protein's heavy atoms for the same systems with respect to the crystal structure.…”

Section: Structure Of the Proteinmentioning

confidence: 96%

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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 Proteinsupporting

confidence: 70%

Section: Structure Of the Proteinmentioning

confidence: 96%

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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“…are denoted in parentheses. Observed to participate in an H bond in at least 1 of the crystal structures of native BPTI (Deisenhofer & Steigemann, 1975;Wlodawer et al, 1984Wlodawer et al, , 1987. versus residue number at pH* 4.6 in (A) Ala at 5 "C (triangles) and 20°C (circles); (B) 130-51; 14-381~5~55 at 5 "C (triangles), 20 "C (circles), and 30 "C (diamonds); and at pH* 4.5 in (C) BPTI at 36 "C (circles) and 56 "C (triangles).…”

Section: Amide Proton Exchangementioning

confidence: 99%

“…In both [5-%]Al, and [30-51; 14-381~5~55, 25 of the 29 backbone amide hydrogens involved in H bonds in the crystal structures of native BPTI (Deisenhofer & Steigemann, 1975;Wlodawer et al, 1984Wlodawer et al, , 1987 are protected from exchange by greater than 100-fold at 5 "C ( Table 1). Of the remaining 4 H bonded residues, three (Phe 4, Lys 26, and Asp 50) are also not protected significantly in native BPTI .…”

Section: Stable Formation Of Native-like Structuresmentioning

confidence: 99%

Hydrogen exchange in BPTI variants that do not share a common disulfide bond

Schulman

Kim

1994

Protein Science

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Bovine pancreatic trypsin inhibitor (BPTI) is stabilized by 3 disulfide bonds, between cysteines 30-5 1, 5-55, and 14-38. To better understand the influence of disulfide bonds on local protein structure and dynamics, we have measured amide proton exchange rates in 2 folded variants of BPTI, [5-%]A], and [30-51; 14-383~5~55, which share no common disulfide bonds. These proteins resemble disulfide-bonded intermediates that accumulate in the BPTI folding pathway. Essentially the same amide hydrogens are protected from exchange in both of the BPTI variants studied here as in native BPTI, demonstrating that the variants adopt fully folded, native-like structures in solution, However, the most highly protected amide protons in each variant differ, and are contained within the sequences of previously studied peptide models of related BPTI foldiing intermediates containing either the 5-55 or the 30-51 disulfide bond.

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“…The first detailed structural studies of [30-5 I] (Deisenhofer & Steigemann, 1975;Wlodawer et al, 1984;Berndt et al, 1992). The terminal residues and the cysteine residues involved in disulfide bonds are labeled.…”

mentioning

confidence: 99%

Formation of a native‐like subdomain in a partially folded intermediate of bovine pancreatic trypsin inhibitor

1994

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In the folding of bovine pancreatic trypsin inhibitor (BPTI), the single-disulfide intermediate [30-511 plays a key role. We have investigated a recombinant analog of [30-511 using 2-dimensional nuclear magnetic resonance (2D-NMR). This recombinant analog, named [30-51lAla, contains a disulfide bond between Cys-30 and Cys-51, but contains alanine in place of the other cysteines in BPTI to prevent the formation of other intermediates. By 2D-NMR, ,,,, consists of 2 regions-one folded and one predominantly unfolded. The folded region resembles a previously characterized peptide model of [30-511, named PaPo, that contains a native-like subdomain with tertiary packing. The unfolded region includes the first 14 N-terminal residues of [30-511 and is as unfolded as an isolated peptide containing these residues. Using protein dissection, we demonstrate that the folded and unfolded regions of The transient nature of most protein folding intermediates precludes a detailed structural study of these intermediates (for review, see Matthews, 1993). Conveniently, however, intermediates in the folding pathway of bovine pancreatic trypsin inhibitor are distinguished covalently by the disulfide bonds that they contain (Creighton, 1977;Creighton & Goldenberg, 1984;Weissman & Kim, 1991, 1992a. The covalent nature of these intermediates (Fig. 1) allows them to be trapped readily and characterized in structural detail. Abbreviations: BPTI, bovine pancreatic trypsin inhibitor; COSY, correlation spectroscopy; Gdn. HCI, guanidine hydrochloride; HMQC, heteronuclear multiple quantum coherence; HSMQC, heteronuclear single-multiple quantum coherence; HSQC, heteronuclear single quantum coherence; NOESY, nuclear Overhauser effect spectroscopy; ppm, parts per million; TOCSY, total correlation spectroscopy; 2D-NMR, 2-dimensional NMR.94143-0448.

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Crystallographic refinement of the structure of bovine pancreatic trypsin inhibitor at l.5 Å resolution

Cited by 582 publications

References 9 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

Hydrogen exchange in BPTI variants that do not share a common disulfide bond

Formation of a native‐like subdomain in a partially folded intermediate of bovine pancreatic trypsin inhibitor

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