Literature DB >> 28448715

Acyl Carrier Protein Cyanylation Delivers a Ketoacyl Synthase-Carrier Protein Cross-Link.

Grace A R Thiele1, Connie P Friedman1, Kathleen J S Tsai1, Joris Beld2, Casey H Londergan1, Louise K Charkoudian1.   

Abstract

Acyl carrier proteins (ACPs) are central hubs in polyketide and fatty acid biosynthetic pathways, but the fast motions of the ACP's phosphopantetheine (Ppant) arm make its conformational dynamics difficult to capture using traditional spectroscopic approaches. Here we report that converting the terminal thiol of Escherichia coli ACP's Ppant arm into a thiocyanate activates this site to form a selective cross-link with the active site cysteine of its partner ketoacyl synthase (FabF). The reaction releases a cyanide anion, which can be detected by infrared spectroscopy. This represents a practical and generalizable method for obtaining and visualizing ACP-protein complexes relevant to biocatalysis and will be valuable in future structural and engineering studies.

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Year:  2017        PMID： 28448715      PMCID： PMC5590888          DOI： 10.1021/acs.biochem.7b00219

Source DB:  PubMed          Journal:  Biochemistry        ISSN： 0006-2960            Impact factor:   3.162


  15 in total

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Authors:  Andrew S Worthington; Douglas F Porter; Michael D Burkart
Journal:  Org Biomol Chem       Date:  2010-04-21       Impact factor: 3.876

3.  Structure of the complex between the antibiotic cerulenin and its target, beta-ketoacyl-acyl carrier protein synthase.

Authors:  M Moche; G Schneider; P Edwards; K Dehesh; Y Lindqvist
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4.  Probing the selectivity and protein·protein interactions of a nonreducing fungal polyketide synthase using mechanism-based crosslinkers.

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Journal:  Chem Biol       Date:  2013-08-29

5.  Specific disulfide cross-linking to constrict the mobile carrier domain of nonribosomal peptide synthetases.

Authors:  Michael J Tarry; T Martin Schmeing
Journal:  Protein Eng Des Sel       Date:  2015-02-23       Impact factor: 1.650

6.  Visualizing the chain-flipping mechanism in fatty-acid biosynthesis.

Authors:  Joris Beld; Hu Cang; Michael D Burkart
Journal:  Angew Chem Int Ed Engl       Date:  2014-10-29       Impact factor: 15.336

Review 7.  Using modern tools to probe the structure-function relationship of fatty acid synthases.

Authors:  Kara Finzel; D John Lee; Michael D Burkart
Journal:  Chembiochem       Date:  2015-02-10       Impact factor: 3.164

8.  Investigations of cyanide as an infrared probe of hemeprotein ligand binding sites.

Authors:  S Yoshikawa; D H O'Keeffe; W S Caughey
Journal:  J Biol Chem       Date:  1985-03-25       Impact factor: 5.157

9.  Structural rearrangements of a polyketide synthase module during its catalytic cycle.

Authors:  Jonathan R Whicher; Somnath Dutta; Douglas A Hansen; Wendi A Hale; Joseph A Chemler; Annie M Dosey; Alison R H Narayan; Kristina Håkansson; David H Sherman; Janet L Smith; Georgios Skiniotis
Journal:  Nature       Date:  2014-06-18       Impact factor: 49.962

10.  Probing the phosphopantetheine arm conformations of acyl carrier proteins using vibrational spectroscopy.

Authors:  Matthew N R Johnson; Casey H Londergan; Louise K Charkoudian
Journal:  J Am Chem Soc       Date:  2014-08-04       Impact factor: 15.419
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  4 in total

1.  Molecular basis for interactions between an acyl carrier protein and a ketosynthase.

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2.  Engineered Chimeras Unveil Swappable Modular Features of Fatty Acid and Polyketide Synthase Acyl Carrier Proteins.

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Journal:  Biochemistry       Date:  2022-01-24       Impact factor: 3.321

Review 3.  Trapping interactions between catalytic domains and carrier proteins of modular biosynthetic enzymes with chemical probes.

Authors:  Andrew M Gulick; Courtney C Aldrich
Journal:  Nat Prod Rep       Date:  2018-11-14       Impact factor: 13.423

Review 4.  Probing the structure and function of acyl carrier proteins to unlock the strategic redesign of type II polyketide biosynthetic pathways.

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