Modifications outside the proteinase binding loop in <i>Cucurbita maxima</i> trypsin inhibitor III (CMTI‐III) analogues change the binding energy with bovine β‐trypsin

Jaśkiewicz, Anna; Lis, Katarzyna; Różycki, Jan; Kupryszewski, G.; Rolka, Krzysztof; Ragnarsson, Ulf; Zbyryt, Tomasz; Wilusz, Tadeusz

doi:10.1016/s0014-5793(98)01119-3

Cited by 4 publications

(2 citation statements)

References 18 publications

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“…Due to their small size and unique structure, these inhibitors have been studied extensively. Peptide synthesis ( , ) and synthetic gene expression ( , ) are two convenient routes to their preparation, and have allowed detailed structure−function studies ( , ). All of these features, and also their high stability and rigidity, make these natural compounds very interesting models for the design of inhibitors for other proteases, such as elastase and chymotrypsin.…”

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confidence: 99%

Squash Trypsin Inhibitors fromMomordica cochinchinensisExhibit an Atypical Macrocyclic Structure

et al. 2000

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Three trypsin inhibitors (TIs), from the seeds of the squash Momordica cochinchinensis (MCo), have been isolated and purified using gel filtration, ion exchange chromatography, and reverse-phase HPLC. Their sequences could be determined only after proteolytic cleavages. In the case of MCoTI-I and -II, it was shown that their polypeptide backbones are cyclic, a structure that has never been described in squash TIs. They contain 34 amino acid residues with 3 disulfide bridges and measured molecular masses of 3453.0 and 3480.7, respectively. They are the largest known macrocyclic peptides containing disulfide bridges. Their sequences show strong homology to other squash TIs, suggesting a similar three-dimensional structure and an analogous mechanism of action. A model of MCoTI-II was constructed by analogy to the crystal structure of the complex between bovine trypsin and CMTI-I, indicating that the linker connecting the two termini is flexible and does not impose significant geometrical constraints. This flexibility allows an Asp-Gly peptide bond rearrangement to occur in this region, giving rise to two isoforms of MCoTI-II. Although the importance of cyclization is not clear, it might confer increased stability and resistance to proteolysis. A minor species, MCoTI-III, was also characterized as containing 30 amino acid residues with a molecular mass of 3379.6. This component possesses a linear backbone with a blocked N-terminus. MCoTIs represent interesting candidates for drug design, either by changing their specificity of inhibition or by using their structure as natural scaffolds bearing new binding activities.

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Squash Trypsin Inhibitors fromMomordica cochinchinensisExhibit an Atypical Macrocyclic Structure

et al. 2000

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“…Position 41 is located close to the catalytic pocket (Figs. 6a and 7b) and is known to interact with trypsin inhibitors (Jaśkiewicz et al, 1998;Batt et al, 2015;Cui et al, 2015). In 98.2% of the cases it is a phenylalanine.…”

Section: Application To the Detection Of Strained Residues With Potenmentioning

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A distance geometry-based description and validation of protein main-chain conformation

Pereira

Lamzin

2017

Int Union Crystallogr J

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Understanding the protein main-chain conformational space forms the basis for the modelling of protein structures and for the validation of models derived from structural biology techniques. Presented here is a novel idea for a threedimensional distance geometry-based metric to account for the fine details of protein backbone conformations. The metrics are computed for dipeptide units, defined as blocks of C iÀ1 -O iÀ1 -C i -O i -C i+1 atoms, by obtaining the eigenvalues of their Euclidean distance matrices. These were computed for $1.3 million dipeptide units collected from nonredundant good-quality structures in the Protein Data Bank and subjected to principal component analysis. The resulting new Euclidean orthogonal three-dimensional space (DipSpace) allows a probabilistic description of protein backbone geometry. The three axes of the DipSpace describe the local extension of the dipeptide unit structure, its twist and its bend. By using a higher-dimensional metric, the method is efficient for the identification of C atoms in an unlikely or unusual geometrical environment, and its use for both local and overall validation of protein models is demonstrated. It is also shown, for the example of trypsin proteases, that the detection of unusual conformations that are conserved among the structures of this protein family may indicate geometrically strained residues of potentially functional importance.

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Design, Chemical Synthesis and Kinetic Studies of Trypsin Chromogenic Substrates Based on the Proteinase Binding Loop of Cucurbita maxima Trypsin Inhibitor (CMTI-III)

Lesner

Brzozowski²,

Kupryszewski³

et al. 2000

Biochemical and Biophysical Research Communications

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Modifications outside the proteinase binding loop in Cucurbita maxima trypsin inhibitor III (CMTI‐III) analogues change the binding energy with bovine β‐trypsin

Cited by 4 publications

References 18 publications

Squash Trypsin Inhibitors fromMomordica cochinchinensisExhibit an Atypical Macrocyclic Structure

Squash Trypsin Inhibitors fromMomordica cochinchinensisExhibit an Atypical Macrocyclic Structure

A distance geometry-based description and validation of protein main-chain conformation

Design, Chemical Synthesis and Kinetic Studies of Trypsin Chromogenic Substrates Based on the Proteinase Binding Loop of Cucurbita maxima Trypsin Inhibitor (CMTI-III)

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