Modifying the Thioester Linkage Affects the Structure of the Acyl Carrier Protein.
Acyl carrier protein
NMR
molecular dynamics
protein interactions
protein structures
Journal
Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543
Informations de publication
Date de publication:
05 08 2019
05 08 2019
Historique:
received:
28
03
2019
revised:
17
05
2019
pubmed:
30
5
2019
medline:
23
9
2020
entrez:
30
5
2019
Statut:
ppublish
Résumé
At the center of many complex biosynthetic pathways, the acyl carrier protein (ACP) shuttles substrates to appropriate enzymatic partners to produce fatty acids and polyketides. Carrier proteins covalently tether their cargo via a thioester linkage to a phosphopantetheine cofactor. Due to the labile nature of this linkage, chemoenzymatic methods have been developed that involve replacement of the thioester with a more stable amide or ester bond. We explored the importance of the thioester bond to the structure of the carrier protein by using solution NMR spectroscopy and molecular dynamics simulations. Remarkably, the replacement of sulfur with other heteroatoms results in significant structural changes, thus suggesting more rigorous selections of isosteric substitutes is needed.
Identifiants
pubmed: 31140212
doi: 10.1002/anie.201903815
pmc: PMC6663632
mid: NIHMS1033056
doi:
Substances chimiques
Carrier Proteins
0
Esters
0
Sulfhydryl Compounds
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
10888-10892Subventions
Organisme : Division of Graduate Education
ID : DGE-1650112
Pays : International
Organisme : NIGMS NIH HHS
ID : K12 GM068524
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM031749
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM095970
Pays : United States
Informations de copyright
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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