7FC0

Reconstitution of MbnABC complex from Rugamonas rubra ATCC-43154 (GroupIII)

Summary for 7FC0

• Entry DOI: 10.2210/pdb7fc0/pdb
• Descriptor: RrMbnA precosur peptide, Methanobactin biosynthesis cassette protein MbnB, Methanobactin biosynthesis cassette protein MbnC, ... (6 entities in total)
• Functional Keywords: fe binding protein, mbnabc complex, methanobactin., metal binding protein
• Biological source: Rugamonas rubra; More
• Total number of polymer chains: 6
• Total formula weight: 109686.04

Authors

Chao, D.,Zhaolin, L.,Shoujie, L.,Li, Z.,Dan, Z.,Ying, J.,Wei, C. (deposition date: 2021-07-13, release date: 2022-03-16, Last modification date: 2023-11-29)

Primary citation

Dou, C.,Long, Z.,Li, S.,Zhou, D.,Jin, Y.,Zhang, L.,Zhang, X.,Zheng, Y.,Li, L.,Zhu, X.,Liu, Z.,He, S.,Yan, W.,Yang, L.,Xiong, J.,Fu, X.,Qi, S.,Ren, H.,Chen, S.,Dai, L.,Wang, B.,Cheng, W.
Crystal structure and catalytic mechanism of the MbnBC holoenzyme required for methanobactin biosynthesis.
Cell Res., 32:302-314, 2022

PubMed Abstract: Methanobactins (Mbns) are a family of copper-binding peptides involved in copper uptake by methanotrophs, and are potential therapeutic agents for treating diseases characterized by disordered copper accumulation. Mbns are produced via modification of MbnA precursor peptides at cysteine residues catalyzed by the core biosynthetic machinery containing MbnB, an iron-dependent enzyme, and MbnC. However, mechanistic details underlying the catalysis of the MbnBC holoenzyme remain unclear. Here, we present crystal structures of MbnABC complexes from two distinct species, revealing that the leader peptide of the substrate MbnA binds MbnC for recruitment of the MbnBC holoenzyme, while the core peptide of MbnA resides in the catalytic cavity created by the MbnB-MbnC interaction which harbors a unique tri-iron cluster. Ligation of the substrate sulfhydryl group to the tri-iron center achieves a dioxygen-dependent reaction for oxazolone-thioamide installation. Structural analysis of the MbnABC complexes together with functional investigation of MbnB variants identified a conserved catalytic aspartate residue as a general base required for MbnBC-mediated MbnA modification. Together, our study reveals the similar architecture and function of MbnBC complexes from different species, demonstrating an evolutionarily conserved catalytic mechanism of the MbnBC holoenzymes.

PubMed: 35110668
DOI: 10.1038/s41422-022-00620-2

Experimental method

X-RAY DIFFRACTION (2.643 Å)