TU Darmstadt / ULB / TUbiblio

Decoding the Papain Inhibitor from Streptomyces mobaraensis as Being Hydroxylated Chymostatin Derivatives: Purification, Structure Analysis, and Putative Biosynthetic Pathway.

Juettner, Norbert E. ; Bogen, Jan P. ; Bauer, Tobias A. ; Knapp, Stefan ; Pfeifer, Felicitas ; Huettenhain, Stefan H. ; Meusinger, Reinhard ; Kraemer, Andreas ; Fuchsbauer, Hans-Lothar (2020)
Decoding the Papain Inhibitor from Streptomyces mobaraensis as Being Hydroxylated Chymostatin Derivatives: Purification, Structure Analysis, and Putative Biosynthetic Pathway.
In: Journal of natural products, 83 (10)
doi: 10.1021/acs.jnatprod.0c00201
Article, Bibliographie

Abstract

produces the papain inhibitor SPI consisting of a 12 kDa protein and small active compounds (SPI). Purification of the papain inhibitory compounds resulted in four diverse chymostatin derivatives that were characterized by NMR and MS analysis. Chymostatins are hydrophobic tetrapeptide aldehydes from streptomycetes, e.g., and , that reverse chymosin-mediated angiotensin activation and inhibit other serine and cysteine proteases. Chymotrypsin and papain were both inhibited by the SPI compounds in the low nanomolar range. SPI differs from the characterized chymostatins by the exchange of phenylalanine for tyrosine. The crystal structure of one of these chymostatin variants confirmed its molecular structure and revealed a S-configured hemithioacetal bond with the catalytic Cys25 thiolate as well as close interactions with hydrophobic S1 and S2 subsite amino acids. A model for chymostatin biosynthesis is provided based on the discovery of clustered genes encoding several putative nonribosomal peptide synthetases; among them, there is the unusual CstF enzyme that accommodates two canonical amino acid activation domains as well as three peptide carrier protein domains.

Item Type: Article
Erschienen: 2020
Creators: Juettner, Norbert E. ; Bogen, Jan P. ; Bauer, Tobias A. ; Knapp, Stefan ; Pfeifer, Felicitas ; Huettenhain, Stefan H. ; Meusinger, Reinhard ; Kraemer, Andreas ; Fuchsbauer, Hans-Lothar
Type of entry: Bibliographie
Title: Decoding the Papain Inhibitor from Streptomyces mobaraensis as Being Hydroxylated Chymostatin Derivatives: Purification, Structure Analysis, and Putative Biosynthetic Pathway.
Language: English
Date: October 2020
Journal or Publication Title: Journal of natural products
Volume of the journal: 83
Issue Number: 10
DOI: 10.1021/acs.jnatprod.0c00201
Abstract:

produces the papain inhibitor SPI consisting of a 12 kDa protein and small active compounds (SPI). Purification of the papain inhibitory compounds resulted in four diverse chymostatin derivatives that were characterized by NMR and MS analysis. Chymostatins are hydrophobic tetrapeptide aldehydes from streptomycetes, e.g., and , that reverse chymosin-mediated angiotensin activation and inhibit other serine and cysteine proteases. Chymotrypsin and papain were both inhibited by the SPI compounds in the low nanomolar range. SPI differs from the characterized chymostatins by the exchange of phenylalanine for tyrosine. The crystal structure of one of these chymostatin variants confirmed its molecular structure and revealed a S-configured hemithioacetal bond with the catalytic Cys25 thiolate as well as close interactions with hydrophobic S1 and S2 subsite amino acids. A model for chymostatin biosynthesis is provided based on the discovery of clustered genes encoding several putative nonribosomal peptide synthetases; among them, there is the unusual CstF enzyme that accommodates two canonical amino acid activation domains as well as three peptide carrier protein domains.

Identification Number: pmid:32998509
Divisions: 10 Department of Biology
10 Department of Biology > Microbiology and Archaea
Date Deposited: 12 Oct 2020 10:01
Last Modified: 29 Dec 2020 08:06
PPN:
Export:
Suche nach Titel in: TUfind oder in Google
Send an inquiry Send an inquiry

Options (only for editors)
Show editorial Details Show editorial Details