3RG2

Structure of a two-domain NRPS fusion protein containing the EntE adenylation domain and EntB aryl-carrier protein from enterobactin biosynthesis

Summary for 3RG2

• Entry DOI: 10.2210/pdb3rg2/pdb
• Descriptor: Enterobactin synthase component E (entE), 2,3-dihydro-2,3-dihydroxybenzoate synthetase, isochroismatase (Entb), 5'-deoxy-5'-({[2-(2-hydroxyphenyl)ethyl]sulfonyl}amino)adenosine, 4'-PHOSPHOPANTETHEINE, ... (4 entities in total)
• Functional Keywords: adenylate-forming enzymes, anl superfamily, non-ribosomal peptide synthetase carrier protein function, nrps adenylation domain acyl carrier protein, 4'phosphopantetheinylation 4'pp cofactor, ligase
• Biological source: Escherichia coli; More
• Total number of polymer chains: 10
• Total formula weight: 694555.15

Authors

Sundlov, J.A.,Gulick, A.M. (deposition date: 2011-04-07, release date: 2012-03-07, Last modification date: 2023-09-13)

Primary citation

Sundlov, J.A.,Shi, C.,Wilson, D.J.,Aldrich, C.C.,Gulick, A.M.
Structural and Functional Investigation of the Intermolecular Interaction between NRPS Adenylation and Carrier Protein Domains.
Chem.Biol., 19:188-198, 2012

PubMed Abstract: Nonribosomal peptide synthetases (NRPSs) are modular proteins that produce peptide antibiotics and siderophores. These enzymes act as catalytic assembly lines where substrates, covalently bound to integrated carrier domains, are delivered to adjacent catalytic domains. The carrier domains are initially loaded by adenylation domains, which use two distinct conformations to catalyze sequentially the adenylation of the substrate and the thioesterification of the pantetheine cofactor. We have used a mechanism-based inhibitor to determine the crystal structure of an engineered adenylation-carrier domain protein illustrating the intermolecular interaction between the adenylation and carrier domains. This structure enabled directed mutations to improve the interaction between nonnative partner proteins. Comparison with prior NRPS adenylation domain structures provides insights into the assembly line dynamics of these modular enzymes.

PubMed: 22365602
DOI: 10.1016/j.chembiol.2011.11.013

Experimental method

X-RAY DIFFRACTION (3.1 Å)