4ZA1
Crystal Structure of NosA Involved in Nosiheptide Biosynthesis
Summary for 4ZA1
| Entry DOI | 10.2210/pdb4za1/pdb |
| Descriptor | NosA, 2,3-DIHYDROXY-1,4-DITHIOBUTANE (3 entities in total) |
| Functional Keywords | beta barrel, transferase |
| Biological source | Streptomyces actuosus |
| Total number of polymer chains | 3 |
| Total formula weight | 49060.95 |
| Authors | |
| Primary citation | Liu, S.,Guo, H.,Zhang, T.,Han, L.,Yao, P.,Zhang, Y.,Rong, N.,Yu, Y.,Lan, W.,Wang, C.,Ding, J.,Wang, R.,Liu, W.,Cao, C. Structure-based Mechanistic Insights into Terminal Amide Synthase in Nosiheptide-Represented Thiopeptides Biosynthesis Sci Rep, 5:12744-12744, 2015 Cited by PubMed Abstract: Nosiheptide is a parent compound of thiopeptide family that exhibit potent activities against various bacterial pathogens. Its C-terminal amide formation is catalyzed by NosA, which is an unusual strategy for maturating certain thiopeptides by processing their precursor peptides featuring a serine extension. We here report the crystal structure of truncated NosA1-111 variant, revealing three key elements, including basic lysine 49 (K49), acidic glutamic acid 101 (E101) and flexible C-terminal loop NosA112-151, are crucial to the catalytic terminal amide formation in nosiheptide biosynthesis. The side-chain of residue K49 and the C-terminal loop fasten the substrate through hydrogen bonds and hydrophobic interactions. The side-chain of residue E101 enhances nucleophilic attack of H2O to the methyl imine intermediate, leading to Cα-N bond cleavage and nosiheptide maturation. The sequence alignment of NosA and its homologs NocA, PbtH, TpdK and BerI, and the enzymatic assay suggest that the mechanistic studies on NosA present an intriguing paradigm about how NosA family members function during thiopeptide biosynthesis. PubMed: 26244829DOI: 10.1038/srep12744 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
Download full validation report
