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
Artikel, Bibliographie
Kurzbeschreibung (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.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2020 |
| Autor(en): | Juettner, Norbert E. ; Bogen, Jan P. ; Bauer, Tobias A. ; Knapp, Stefan ; Pfeifer, Felicitas ; Huettenhain, Stefan H. ; Meusinger, Reinhard ; Kraemer, Andreas ; Fuchsbauer, Hans-Lothar |
| Art des Eintrags: | Bibliographie |
| Titel: | Decoding the Papain Inhibitor from Streptomyces mobaraensis as Being Hydroxylated Chymostatin Derivatives: Purification, Structure Analysis, and Putative Biosynthetic Pathway. |
| Sprache: | Englisch |
| Publikationsjahr: | Oktober 2020 |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Journal of natural products |
| Jahrgang/Volume einer Zeitschrift: | 83 |
| (Heft-)Nummer: | 10 |
| DOI: | 10.1021/acs.jnatprod.0c00201 |
| Kurzbeschreibung (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. |
| ID-Nummer: | pmid:32998509 |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Microbiology and Archaea |
| Hinterlegungsdatum: | 12 Okt 2020 10:01 |
| Letzte Änderung: | 29 Dez 2020 08:06 |
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