The structure of MadC from Clostridium maddingley reveals new insights into class I lanthipeptide cyclases
The rapid emergence of microbial multi-resistance against antibiotics has led to intense search for alternatives. One of these alternatives are ribosomally synthesized and post-translationally modified peptides (RiPPs), especially lantibiotics. They are active in a low nanomolar range and their high...
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| Format: | Article |
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Frontiers Media S.A.
2023-01-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fmicb.2022.1057217/full |
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| author | C. Vivien Knospe Michael Kamel Olivia Spitz Astrid Hoeppner Stefanie Galle Jens Reiners Alexej Kedrov Sander H. J. Smits Sander H. J. Smits Lutz Schmitt |
| author_facet | C. Vivien Knospe Michael Kamel Olivia Spitz Astrid Hoeppner Stefanie Galle Jens Reiners Alexej Kedrov Sander H. J. Smits Sander H. J. Smits Lutz Schmitt |
| author_sort | C. Vivien Knospe |
| collection | DOAJ |
| description | The rapid emergence of microbial multi-resistance against antibiotics has led to intense search for alternatives. One of these alternatives are ribosomally synthesized and post-translationally modified peptides (RiPPs), especially lantibiotics. They are active in a low nanomolar range and their high stability is due to the presence of characteristic (methyl-) lanthionine rings, which makes them promising candidates as bacteriocides. However, innate resistance against lantibiotics exists in nature, emphasizing the need for artificial or tailor-made lantibiotics. Obviously, such an approach requires an in-depth mechanistic understanding of the modification enzymes, which catalyze the formation of (methyl-)lanthionine rings. Here, we determined the structure of a class I cyclase (MadC), involved in the modification of maddinglicin (MadA) via X-ray crystallography at a resolution of 1.7 Å, revealing new insights about the structural composition of the catalytical site. These structural features and substrate binding were analyzed by mutational analyses of the leader peptide as well as of the cyclase, shedding light into the mode of action of MadC. |
| first_indexed | 2024-04-10T22:18:21Z |
| format | Article |
| id | doaj.art-305800b6f87e4c338dd295b22eaecb64 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-10T22:18:21Z |
| publishDate | 2023-01-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-305800b6f87e4c338dd295b22eaecb642023-01-18T05:23:57ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2023-01-011310.3389/fmicb.2022.10572171057217The structure of MadC from Clostridium maddingley reveals new insights into class I lanthipeptide cyclasesC. Vivien Knospe0Michael Kamel1Olivia Spitz2Astrid Hoeppner3Stefanie Galle4Jens Reiners5Alexej Kedrov6Sander H. J. Smits7Sander H. J. Smits8Lutz Schmitt9Institute of Biochemistry, Heinrich Heine University Düsseldorf, Düsseldorf, GermanySynthetic Membrane Systems, Institute of Biochemistry, Heinrich Heine University Düsseldorf, Düsseldorf, GermanyInstitute of Biochemistry, Heinrich Heine University Düsseldorf, Düsseldorf, GermanyCenter for Structural Studies, Heinrich Heine University Düsseldorf, Düsseldorf, GermanyCenter for Structural Studies, Heinrich Heine University Düsseldorf, Düsseldorf, GermanyCenter for Structural Studies, Heinrich Heine University Düsseldorf, Düsseldorf, GermanySynthetic Membrane Systems, Institute of Biochemistry, Heinrich Heine University Düsseldorf, Düsseldorf, GermanyInstitute of Biochemistry, Heinrich Heine University Düsseldorf, Düsseldorf, GermanyCenter for Structural Studies, Heinrich Heine University Düsseldorf, Düsseldorf, GermanyInstitute of Biochemistry, Heinrich Heine University Düsseldorf, Düsseldorf, GermanyThe rapid emergence of microbial multi-resistance against antibiotics has led to intense search for alternatives. One of these alternatives are ribosomally synthesized and post-translationally modified peptides (RiPPs), especially lantibiotics. They are active in a low nanomolar range and their high stability is due to the presence of characteristic (methyl-) lanthionine rings, which makes them promising candidates as bacteriocides. However, innate resistance against lantibiotics exists in nature, emphasizing the need for artificial or tailor-made lantibiotics. Obviously, such an approach requires an in-depth mechanistic understanding of the modification enzymes, which catalyze the formation of (methyl-)lanthionine rings. Here, we determined the structure of a class I cyclase (MadC), involved in the modification of maddinglicin (MadA) via X-ray crystallography at a resolution of 1.7 Å, revealing new insights about the structural composition of the catalytical site. These structural features and substrate binding were analyzed by mutational analyses of the leader peptide as well as of the cyclase, shedding light into the mode of action of MadC.https://www.frontiersin.org/articles/10.3389/fmicb.2022.1057217/fulllanthipeptidecyclasesX-ray structureclass I lantibioticITC |
| spellingShingle | C. Vivien Knospe Michael Kamel Olivia Spitz Astrid Hoeppner Stefanie Galle Jens Reiners Alexej Kedrov Sander H. J. Smits Sander H. J. Smits Lutz Schmitt The structure of MadC from Clostridium maddingley reveals new insights into class I lanthipeptide cyclases Frontiers in Microbiology lanthipeptide cyclases X-ray structure class I lantibiotic ITC |
| title | The structure of MadC from Clostridium maddingley reveals new insights into class I lanthipeptide cyclases |
| title_full | The structure of MadC from Clostridium maddingley reveals new insights into class I lanthipeptide cyclases |
| title_fullStr | The structure of MadC from Clostridium maddingley reveals new insights into class I lanthipeptide cyclases |
| title_full_unstemmed | The structure of MadC from Clostridium maddingley reveals new insights into class I lanthipeptide cyclases |
| title_short | The structure of MadC from Clostridium maddingley reveals new insights into class I lanthipeptide cyclases |
| title_sort | structure of madc from clostridium maddingley reveals new insights into class i lanthipeptide cyclases |
| topic | lanthipeptide cyclases X-ray structure class I lantibiotic ITC |
| url | https://www.frontiersin.org/articles/10.3389/fmicb.2022.1057217/full |
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