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Structural insights into serine protease inhibition by a marine invertebrate BPTI Kunitz-type inhibitor.

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Structural insights into serine protease inhibition by a marine invertebrate BPTI Kunitz-type inhibitor. / García-Fernández, Rossana; Pons, Tirso; Perbandt, Markus; Valiente, Pedro A; Talavera, Ariel; González-González, Yamile; Rehders, Dirk; Chávez, María A; Betzel, Christian; Redecke, Lars.

In: J STRUCT BIOL, Vol. 180, No. 2, 2, 2012, p. 271-279.

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

Harvard

García-Fernández, R, Pons, T, Perbandt, M, Valiente, PA, Talavera, A, González-González, Y, Rehders, D, Chávez, MA, Betzel, C & Redecke, L 2012, 'Structural insights into serine protease inhibition by a marine invertebrate BPTI Kunitz-type inhibitor.', J STRUCT BIOL, vol. 180, no. 2, 2, pp. 271-279. <http://www.ncbi.nlm.nih.gov/pubmed/22975140?dopt=Citation>

APA

García-Fernández, R., Pons, T., Perbandt, M., Valiente, P. A., Talavera, A., González-González, Y., Rehders, D., Chávez, M. A., Betzel, C., & Redecke, L. (2012). Structural insights into serine protease inhibition by a marine invertebrate BPTI Kunitz-type inhibitor. J STRUCT BIOL, 180(2), 271-279. [2]. http://www.ncbi.nlm.nih.gov/pubmed/22975140?dopt=Citation

Vancouver

García-Fernández R, Pons T, Perbandt M, Valiente PA, Talavera A, González-González Y et al. Structural insights into serine protease inhibition by a marine invertebrate BPTI Kunitz-type inhibitor. J STRUCT BIOL. 2012;180(2):271-279. 2.

Bibtex

@article{d630b07a5e60400a814418f947c87755,
title = "Structural insights into serine protease inhibition by a marine invertebrate BPTI Kunitz-type inhibitor.",
abstract = "Proteins isolated from marine invertebrates are frequently characterized by exceptional structural and functional properties. ShPI-1, a BPTI Kunitz-type inhibitor from the Caribbean Sea anemone Stichodactyla helianthus, displays activity not only against serine-, but also against cysteine-, and aspartate proteases. As an initial step to evaluate the molecular basis of its activities, we describe the crystallographic structure of ShPI-1 in complex with the serine protease bovine pancreatic trypsin at 1.7{\AA} resolution. The overall structure and the important enzyme-inhibitor interactions of this first invertebrate BPTI-like Kunitz-type inhibitor:trypsin complex remained largely conserved compared to mammalian BPTI-Kunitz inhibitor complexes. However, a prominent stabilizing role within the interface was attributed to arginine at position P3. Binding free-energy calculations indicated a 10-fold decrease for the inhibitor affinity against trypsin, if the P3 residue of ShPI-1 is mutated to alanine. Together with the increased role of Arg(11) at P3 position, slightly reduced interactions at the prime side (Pn') of the primary binding loop and at the secondary binding loop of ShPI-1 were detected. In addition, the structure provides important information for site directed mutagenesis to further optimize the activity of rShPI-1A for biotechnological applications.",
keywords = "Animals, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Cattle, Mutagenesis, Site-Directed, Crystallography, X-Ray, Sea Anemones, Serine Endopeptidases/*chemistry/*metabolism, Serine Proteinase Inhibitors/*chemistry/*pharmacology, Trypsin/*metabolism, Animals, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Cattle, Mutagenesis, Site-Directed, Crystallography, X-Ray, Sea Anemones, Serine Endopeptidases/*chemistry/*metabolism, Serine Proteinase Inhibitors/*chemistry/*pharmacology, Trypsin/*metabolism",
author = "Rossana Garc{\'i}a-Fern{\'a}ndez and Tirso Pons and Markus Perbandt and Valiente, {Pedro A} and Ariel Talavera and Yamile Gonz{\'a}lez-Gonz{\'a}lez and Dirk Rehders and Ch{\'a}vez, {Mar{\'i}a A} and Christian Betzel and Lars Redecke",
year = "2012",
language = "English",
volume = "180",
pages = "271--279",
journal = "J STRUCT BIOL",
issn = "1047-8477",
publisher = "Academic Press Inc.",
number = "2",

}

RIS

TY - JOUR

T1 - Structural insights into serine protease inhibition by a marine invertebrate BPTI Kunitz-type inhibitor.

AU - García-Fernández, Rossana

AU - Pons, Tirso

AU - Perbandt, Markus

AU - Valiente, Pedro A

AU - Talavera, Ariel

AU - González-González, Yamile

AU - Rehders, Dirk

AU - Chávez, María A

AU - Betzel, Christian

AU - Redecke, Lars

PY - 2012

Y1 - 2012

N2 - Proteins isolated from marine invertebrates are frequently characterized by exceptional structural and functional properties. ShPI-1, a BPTI Kunitz-type inhibitor from the Caribbean Sea anemone Stichodactyla helianthus, displays activity not only against serine-, but also against cysteine-, and aspartate proteases. As an initial step to evaluate the molecular basis of its activities, we describe the crystallographic structure of ShPI-1 in complex with the serine protease bovine pancreatic trypsin at 1.7Å resolution. The overall structure and the important enzyme-inhibitor interactions of this first invertebrate BPTI-like Kunitz-type inhibitor:trypsin complex remained largely conserved compared to mammalian BPTI-Kunitz inhibitor complexes. However, a prominent stabilizing role within the interface was attributed to arginine at position P3. Binding free-energy calculations indicated a 10-fold decrease for the inhibitor affinity against trypsin, if the P3 residue of ShPI-1 is mutated to alanine. Together with the increased role of Arg(11) at P3 position, slightly reduced interactions at the prime side (Pn') of the primary binding loop and at the secondary binding loop of ShPI-1 were detected. In addition, the structure provides important information for site directed mutagenesis to further optimize the activity of rShPI-1A for biotechnological applications.

AB - Proteins isolated from marine invertebrates are frequently characterized by exceptional structural and functional properties. ShPI-1, a BPTI Kunitz-type inhibitor from the Caribbean Sea anemone Stichodactyla helianthus, displays activity not only against serine-, but also against cysteine-, and aspartate proteases. As an initial step to evaluate the molecular basis of its activities, we describe the crystallographic structure of ShPI-1 in complex with the serine protease bovine pancreatic trypsin at 1.7Å resolution. The overall structure and the important enzyme-inhibitor interactions of this first invertebrate BPTI-like Kunitz-type inhibitor:trypsin complex remained largely conserved compared to mammalian BPTI-Kunitz inhibitor complexes. However, a prominent stabilizing role within the interface was attributed to arginine at position P3. Binding free-energy calculations indicated a 10-fold decrease for the inhibitor affinity against trypsin, if the P3 residue of ShPI-1 is mutated to alanine. Together with the increased role of Arg(11) at P3 position, slightly reduced interactions at the prime side (Pn') of the primary binding loop and at the secondary binding loop of ShPI-1 were detected. In addition, the structure provides important information for site directed mutagenesis to further optimize the activity of rShPI-1A for biotechnological applications.

KW - Animals

KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

KW - Cattle

KW - Mutagenesis, Site-Directed

KW - Crystallography, X-Ray

KW - Sea Anemones

KW - Serine Endopeptidases/chemistry/metabolism

KW - Serine Proteinase Inhibitors/chemistry/pharmacology

KW - Trypsin/metabolism

KW - Animals

KW - Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

KW - Cattle

KW - Mutagenesis, Site-Directed

KW - Crystallography, X-Ray

KW - Sea Anemones

KW - Serine Endopeptidases/chemistry/metabolism

KW - Serine Proteinase Inhibitors/chemistry/pharmacology

KW - Trypsin/metabolism

M3 - SCORING: Journal article

VL - 180

SP - 271

EP - 279

JO - J STRUCT BIOL

JF - J STRUCT BIOL

SN - 1047-8477

IS - 2

M1 - 2

ER -