7XYO

Crystal Structure of a M61 aminopeptidase family member from Myxococcus fulvus

Summary for 7XYO

• Entry DOI: 10.2210/pdb7xyo/pdb
• Descriptor: Aminopeptidase M61, TETRAETHYLENE GLYCOL, HEXAETHYLENE GLYCOL, ... (5 entities in total)
• Functional Keywords: aminopeptidase m61, lantipeptide, ripps, lanthipeptide, synergistic cyclization, peptidase, hydrolase
• Biological source: Myxococcus fulvus
• Total number of polymer chains: 2
• Total formula weight: 124695.59

Authors

Chen, X.,Wang, X.,Huo, L.,Wu, D. (deposition date: 2022-06-02, release date: 2023-06-07, Last modification date: 2023-10-11)

Primary citation

Wang, X.,Chen, X.,Wang, Z.J.,Zhuang, M.,Zhong, L.,Fu, C.,Garcia, R.,Muller, R.,Zhang, Y.,Yan, J.,Wu, D.,Huo, L.
Discovery and Characterization of a Myxobacterial Lanthipeptide with Unique Biosynthetic Features and Anti-inflammatory Activity.
J.Am.Chem.Soc., 145:16924-16937, 2023

PubMed Abstract: The genomes of myxobacteria harbor a variety of biosynthetic gene clusters encoding numerous secondary metabolites, including ribosomally synthesized and post-translationally modified peptides (RiPPs) with diverse chemical structures and biological activities. However, the biosynthetic potential of RiPPs from myxobacteria remains barely explored. Herein, we report a novel myxobacteria lanthipeptide myxococin identified from . Myxococins represent the first example of lanthipeptides, of which the characteristic multiple thioether rings are installed by employing a Class II lanthipeptide synthetase MfuM and a Class I lanthipeptide cyclase MfuC in a cascaded way. Unprecedentedly, we biochemically characterized the first M61 family aminopeptidase MfuP involved in RiPP biosynthesis, demonstrating that MfuP showed the activity of an endopeptidase activity. MfuP is leader-independent but strictly selective for the multibridge structure of myxococin A and responsible for unwrapping two rings via amide bond hydrolysis, yielding myxococin B. Furthermore, the X-ray crystal structure of MfuP and structural analysis, including active-site mutations, are reported. Finally, myxococins are evaluated to exhibit anti-inflammatory activity in lipopolysaccharide-induced macrophages without detectable cytotoxicity.

PubMed: 37466996
DOI: 10.1021/jacs.3c06014

Experimental method

X-RAY DIFFRACTION (2.7 Å)