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Structural basis for the selectivity of the external thioesterase of the surfactin synthetase.
- Source :
- Nature; 8/14/2008, Vol. 454 Issue 7206, p907-911, 5p, 4 Diagrams
- Publication Year :
- 2008
-
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. [ABSTRACT FROM AUTHOR]
- Subjects :
- PEPTIDES
POLYKETIDES
BACTERIA
FUNGI
PHYSICAL biochemistry
BIOCHEMICAL research
Subjects
Details
- Language :
- English
- ISSN :
- 00280836
- Volume :
- 454
- Issue :
- 7206
- Database :
- Complementary Index
- Journal :
- Nature
- Publication Type :
- Academic Journal
- Accession number :
- 33719785
- Full Text :
- https://doi.org/10.1038/nature07161