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High-Resolution Crystal Structure of a Lasso Peptide

Authors

  • Dr. Herbert Nar,

    1. Lead Discovery/Structural Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Straße 65, 88397 Biberach/Riss (Germany), Fax: (+49) (0)7351 832888
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  • Angela Schmid,

    1. Lead Discovery/Structural Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Straße 65, 88397 Biberach/Riss (Germany), Fax: (+49) (0)7351 832888
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  • Dr. Carsten Puder,

    1. Lead Discovery/Structural Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Straße 65, 88397 Biberach/Riss (Germany), Fax: (+49) (0)7351 832888
    2. Current address: Global Function Launch, Boehringer Ingelheim Pharma GmbH & Co. KG, Binger Straße 173, 55216 Ingelheim am Rhein (Germany)
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  • Dr. Olivier Potterat

    1. Lead Discovery/Structural Research, Boehringer Ingelheim Pharma GmbH & Co. KG, Birkendorfer Straße 65, 88397 Biberach/Riss (Germany), Fax: (+49) (0)7351 832888
    2. Current address: University of Basel, Department of Pharmaceutical Biology, Klingelbergstrasse 50, 4056 Basel (Switzerland)
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Abstract

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Have I got noose for you! Lasso peptides are a growing class of bioactive peptides of microbial origin. The first crystal structure of a member of this family, the glucagon receptor antagonist BI-32169, shows that the fold is built predominantly by regular secondary structural elements and a tight network of hydrogen bonds that are partially shielded from solvent by hydrophobic amino acid side chains. This results in an extraordinarily stable structure that is resistant to thermal unfolding or proteolytic digestion, which facilitates its biological function.

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Article Information

DOI

10.1002/cmdc.201000264

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Copyright © 2010 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

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Keywords

  • BI-32169;
  • bioactive peptides;
  • crystal structures;
  • glucagon receptor antagonists;
  • lariat protoknots

Publication History

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  • Manuscript Received:

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  • Number of times cited: 20
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