2RON

The external thioesterase of the Surfactin-Synthetase

Summary for 2RON

• Entry DOI: 10.2210/pdb2ron/pdb
• Descriptor: Surfactin synthetase thioesterase subunit (1 entity in total)
• Functional Keywords: thioesterase, non-ribosomal peptide synthetase, teii, nrps, a/b hydrolase, pcp regeneration, antibiotic biosynthesis, hydrolase, sporulation, stress response
• Biological source: Bacillus subtilis
• Cellular location: Cytoplasm: Q08788
• Total number of polymer chains: 1
• Total formula weight: 27652.54

Authors

Koglin, A.,Lohr, F.,Bernhard, F.,Rogov, V.V.,Frueh, D.P.,Strieter, E.R.,Mofid, M.R.,Guentert, P.,Wagner, G.,Walsh, C.T.,Marahiel, M.A.,Doetsch, V. (deposition date: 2008-04-04, release date: 2008-08-12, Last modification date: 2024-05-01)

Primary citation

Koglin, A.,Lohr, F.,Bernhard, F.,Rogov, V.V.,Frueh, D.P.,Strieter, E.R.,Mofid, M.R.,Guntert, P.,Wagner, G.,Walsh, C.T.,Marahiel, M.A.,Dotsch, V.
Structural basis for the selectivity of the external thioesterase of the surfactin synthetase
Nature, 454:907-911, 2008

PubMed Abstract: Non-ribosomal peptide synthetases (NRPS) and polyketide synthases (PKS) found in bacteria, fungi and plants use two different types of thioesterases for the production of highly active biological compounds. Type I thioesterases (TEI) catalyse the release step from the assembly line of the final product where it is transported from one reaction centre to the next as a thioester linked to a 4'-phosphopantetheine (4'-PP) cofactor that is covalently attached to thiolation (T) domains. The second enzyme involved in the synthesis of these secondary metabolites, the type II thioesterase (TEII), is a crucial repair enzyme for the regeneration of functional 4'-PP cofactors of holo-T domains of NRPS and PKS systems. Mispriming of 4'-PP cofactors by acetyl- and short-chain acyl-residues interrupts the biosynthetic system. This repair reaction is very important, because roughly 80% of CoA, the precursor of the 4'-PP cofactor, is acetylated in bacteria. Here we report the three-dimensional structure of a type II thioesterase from Bacillus subtilis free and in complex with a T domain. Comparison with structures of TEI enzymes shows the basis for substrate selectivity and the different modes of interaction of TEII and TEI enzymes with T domains. Furthermore, we show that the TEII enzyme exists in several conformations of which only one is selected on interaction with its native substrate, a modified holo-T domain.

PubMed: 18704089
DOI: 10.1038/nature07161

Experimental method

SOLUTION NMR