The aspartic proteinase from Saccharomyces cerevisiae folds its own inhibitor into a helix

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

The aspartic proteinase from Saccharomyces cerevisiae folds its own inhibitor into a helix. / Li, Mi; Phylip, Lowri H.; Lees, Wendy E.; Winther, Jakob R.; Dunn, Ben M.; Wlodawer, Alexander; Kay, John; Gustchina, Alla.

In: Nature Structural & Molecular Biology, Vol. 7, No. 2, 2000, p. 113-117.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Li, M, Phylip, LH, Lees, WE, Winther, JR, Dunn, BM, Wlodawer, A, Kay, J & Gustchina, A 2000, 'The aspartic proteinase from Saccharomyces cerevisiae folds its own inhibitor into a helix', Nature Structural & Molecular Biology, vol. 7, no. 2, pp. 113-117. https://doi.org/10.1038/72378

APA

Li, M., Phylip, L. H., Lees, W. E., Winther, J. R., Dunn, B. M., Wlodawer, A., Kay, J., & Gustchina, A. (2000). The aspartic proteinase from Saccharomyces cerevisiae folds its own inhibitor into a helix. Nature Structural & Molecular Biology, 7(2), 113-117. https://doi.org/10.1038/72378

Vancouver

Li M, Phylip LH, Lees WE, Winther JR, Dunn BM, Wlodawer A et al. The aspartic proteinase from Saccharomyces cerevisiae folds its own inhibitor into a helix. Nature Structural & Molecular Biology. 2000;7(2):113-117. https://doi.org/10.1038/72378

Author

Li, Mi ; Phylip, Lowri H. ; Lees, Wendy E. ; Winther, Jakob R. ; Dunn, Ben M. ; Wlodawer, Alexander ; Kay, John ; Gustchina, Alla. / The aspartic proteinase from Saccharomyces cerevisiae folds its own inhibitor into a helix. In: Nature Structural & Molecular Biology. 2000 ; Vol. 7, No. 2. pp. 113-117.

Bibtex

@article{97bac895eea3447e8202872c6d90c9c6,
title = "The aspartic proteinase from Saccharomyces cerevisiae folds its own inhibitor into a helix",
abstract = "Aspartic proteinase A from yeast is specifically and potently inhibited by a small protein called IA3 from Saccharomyces cerevisiae. Although this inhibitor consists of 68 residues, we show that the inhibitory activity resides within the N-terminal half of the molecule. Structures solved at 2.2 and 1.8 A, respectively, for complexes of proteinase A with full-length IA3 and with a truncated form consisting only of residues 2-34, reveal an unprecedented mode of inhibitor-enzyme interactions. Neither form of the free inhibitor has detectable intrinsic secondary structure in solution. However, upon contact with the enzyme, residues 2-32 become ordered and adopt a near-perfect alpha-helical conformation. Thus, the proteinase acts as a folding template, stabilizing the helical conformation in the inhibitor, which results in the potent and specific blockage of the proteolytic activity.",
keywords = "Amino Acid Sequence, Aspartic Acid Endopeptidases, Circular Dichroism, Crystallography, X-Ray, Fungal Proteins, Hydrogen-Ion Concentration, Methionine, Models, Molecular, Molecular Sequence Data, Mutation, Protein Conformation, Protein Folding, Recombinant Proteins, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Trypsin",
author = "Mi Li and Phylip, {Lowri H.} and Lees, {Wendy E.} and Winther, {Jakob R.} and Dunn, {Ben M.} and Alexander Wlodawer and John Kay and Alla Gustchina",
year = "2000",
doi = "10.1038/72378",
language = "English",
volume = "7",
pages = "113--117",
journal = "Nature Structural and Molecular Biology",
issn = "1545-9993",
publisher = "nature publishing group",
number = "2",

}

RIS

TY - JOUR

T1 - The aspartic proteinase from Saccharomyces cerevisiae folds its own inhibitor into a helix

AU - Li, Mi

AU - Phylip, Lowri H.

AU - Lees, Wendy E.

AU - Winther, Jakob R.

AU - Dunn, Ben M.

AU - Wlodawer, Alexander

AU - Kay, John

AU - Gustchina, Alla

PY - 2000

Y1 - 2000

N2 - Aspartic proteinase A from yeast is specifically and potently inhibited by a small protein called IA3 from Saccharomyces cerevisiae. Although this inhibitor consists of 68 residues, we show that the inhibitory activity resides within the N-terminal half of the molecule. Structures solved at 2.2 and 1.8 A, respectively, for complexes of proteinase A with full-length IA3 and with a truncated form consisting only of residues 2-34, reveal an unprecedented mode of inhibitor-enzyme interactions. Neither form of the free inhibitor has detectable intrinsic secondary structure in solution. However, upon contact with the enzyme, residues 2-32 become ordered and adopt a near-perfect alpha-helical conformation. Thus, the proteinase acts as a folding template, stabilizing the helical conformation in the inhibitor, which results in the potent and specific blockage of the proteolytic activity.

AB - Aspartic proteinase A from yeast is specifically and potently inhibited by a small protein called IA3 from Saccharomyces cerevisiae. Although this inhibitor consists of 68 residues, we show that the inhibitory activity resides within the N-terminal half of the molecule. Structures solved at 2.2 and 1.8 A, respectively, for complexes of proteinase A with full-length IA3 and with a truncated form consisting only of residues 2-34, reveal an unprecedented mode of inhibitor-enzyme interactions. Neither form of the free inhibitor has detectable intrinsic secondary structure in solution. However, upon contact with the enzyme, residues 2-32 become ordered and adopt a near-perfect alpha-helical conformation. Thus, the proteinase acts as a folding template, stabilizing the helical conformation in the inhibitor, which results in the potent and specific blockage of the proteolytic activity.

KW - Amino Acid Sequence

KW - Aspartic Acid Endopeptidases

KW - Circular Dichroism

KW - Crystallography, X-Ray

KW - Fungal Proteins

KW - Hydrogen-Ion Concentration

KW - Methionine

KW - Models, Molecular

KW - Molecular Sequence Data

KW - Mutation

KW - Protein Conformation

KW - Protein Folding

KW - Recombinant Proteins

KW - Saccharomyces cerevisiae

KW - Saccharomyces cerevisiae Proteins

KW - Trypsin

U2 - 10.1038/72378

DO - 10.1038/72378

M3 - Journal article

C2 - 10655612

VL - 7

SP - 113

EP - 117

JO - Nature Structural and Molecular Biology

JF - Nature Structural and Molecular Biology

SN - 1545-9993

IS - 2

ER -

ID: 43973904