6MG0

Crystal structure of a 5-domain construct of LgrA in the thiolation state

Summary for 6MG0

• Entry DOI: 10.2210/pdb6mg0/pdb
• Descriptor: Linear gramicidin synthase subunit A, 5'-({[(2R,3R)-3-amino-2-{[2-({N-[(2R)-2-hydroxy-3,3-dimethyl-4-{[oxido(oxo)phosphonio]oxy}butanoyl]-beta-alanyl}amino)ethyl]sulfanyl}-4-methylpentyl]sulfonyl}amino)-5'-deoxyadenosine (2 entities in total)
• Functional Keywords: nonribosomal peptide synthetase, tailoring domain, nrps, enzyme, natural product, linear gramicidin, ligase
• Biological source: Brevibacillus parabrevis
• Total number of polymer chains: 2
• Total formula weight: 393785.75

Authors

Reimer, J.M.,Eivaskhani, M.,Harb, I.,Schmeing, T.M. (deposition date: 2018-09-12, release date: 2019-11-20, Last modification date: 2024-10-30)

Primary citation

Reimer, J.M.,Eivaskhani, M.,Harb, I.,Guarne, A.,Weigt, M.,Schmeing, T.M.
Structures of a dimodular nonribosomal peptide synthetase reveal conformational flexibility.
Science, 366:-, 2019

PubMed Abstract: Nonribosomal peptide synthetases (NRPSs) are biosynthetic enzymes that synthesize natural product therapeutics using a modular synthetic logic, whereby each module adds one aminoacyl substrate to the nascent peptide. We have determined five x-ray crystal structures of large constructs of the NRPS linear gramicidin synthetase, including a structure of a full core dimodule in conformations organized for the condensation reaction and intermodular peptidyl substrate delivery. The structures reveal differences in the relative positions of adjacent modules, which are not strictly coupled to the catalytic cycle and are consistent with small-angle x-ray scattering data. The structures and covariation analysis of homologs allowed us to create mutants that improve the yield of a peptide from a module-swapped dimodular NRPS.

PubMed: 31699907
DOI: 10.1126/science.aaw4388

Experimental method

X-RAY DIFFRACTION (6 Å)