Solution Structure of an Acyl Carrier Protein Domain from a Fungal Type I Polyketide Synthase

P Wattana-Amorn, C Williams, E Płoskoń, RJ Cox, TJ Simpson, J Crosby, MP Crump

Research output: Contribution to journalArticle (Academic Journal)

26 Citations (Scopus)

Abstract

Acyl (peptidyl) carrier protein (ACP or PCP) is a crucial component involved in the transfer of thiol ester-bound intermediates during the biosynthesis of primary and secondary metabolites such its fatty acids, polyketides, and nonribosomal peptides. Although many carrier protein three-dimensional structures have been determined, to date there is no model available for a fungal type I polyketide synthase ACP. Here we report the Solution structure of the norsolorinic acid synthase (NSAS) holo ACP domain that has been excised from the full-length In multifunctional enzyme. NSAS ACP shows similarities in three-dimensional structure with other type I and type II ACPs, consisting of a four-helix bundle with helices I, II, and IV arranged in parallel. The N-terminus of helix III, however, is unusually hydrophobic, and Phe1768 and Leu1770 pack well with the core of the protein. The result is that unlike other carrier proteins, helix III lies almost perpendicular to the three major helices. Helix III is well-derived by numerous NMR-derived distance restraints and may be less flexible than counterparts in type II FAS and PKS ACPs. When the holo ACP is derivatized With it hexanoyl only minor changes are observed between the HSQC spectra of the two ACP species and no NOEs are observed for this hydrophobic acyl group. Along with the mammalian type I FAS, this further strengthens the view that type I ACPs do not show any significant affinity for hydrophobic (nonpolar) chain assembly intermediates attached via the 4'-phosphopantetheine prosthetic group.
Translated title of the contributionSolution Structure of an Acyl Carrier Protein Domain from a Fungal Type I Polyketide Synthase
Original languageEnglish
Pages (from-to)2186 - 2193
Number of pages8
JournalBiochemistry
Volume49
DOIs
Publication statusPublished - Mar 2010

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