The structural organization of substrate loading in iterative polyketide synthases

Autor: Jacob M Kravetz, Philip A. Storm, Jamie R Alley, Timm Maier, Dominik A. Herbst, Callie R. Huitt-Roehl, Craig A. Townsend, Roman P. Jakob
Rok vydání: 2018
Předmět:
0301 basic medicine
Materials science
Stereochemistry
Protein Conformation
Protein domain
Substrate (printing)
Crystallography
X-Ray
Biochemistry
Article
Substrate Specificity
Inorganic Chemistry
03 medical and health sciences
chemistry.chemical_compound
Polyketide
Protein structure
Biosynthesis
Ascomycota
Protein Domains
Structural Biology
Catalytic Domain
Acyl Carrier Protein
Escherichia coli
General Materials Science
Phosphorylation
Physical and Theoretical Chemistry
Molecular Biology
Structural organization
biology
Chemistry
Cryoelectron Microscopy
Substrate (chemistry)
Cell Biology
Condensed Matter Physics
Acyl carrier protein
030104 developmental biology
Cross-Linking Reagents
Chemical engineering
Acyltransferases
Pantetheine
biology.protein
Propionates
Protein Multimerization
Linker
Polyketide Synthases
Zdroj: Acta Crystallographica Section A Foundations and Advances. 74:e28-e28
ISSN: 2053-2733
DOI: 10.1107/s2053273318094792
Popis: Polyketide synthases (PKSs) are microbial multienzymes for the biosynthesis of biologically potent secondary metabolites. Polyketide production is initiated by the loading of a starter unit onto an integral acyl carrier protein (ACP) and its subsequent transfer to the ketosynthase (KS). Initial substrate loading is achieved either by multidomain loading modules or by the integration of designated loading domains, such as starter unit acyltransferases (SAT), whose structural integration into PKS remains unresolved. A crystal structure of the loading/condensing region of the nonreducing PKS CTB1 demonstrates the ordered insertion of a pseudodimeric SAT into the condensing region, which is aided by the SAT-KS linker. Cryo-electron microscopy of the post-loading state trapped by mechanism-based crosslinking of ACP to KS reveals asymmetry across the CTB1 loading/-condensing region, in accord with preferential 1:2 binding stoichiometry. These results are critical for re-engineering the loading step in polyketide biosynthesis and support functional relevance of asymmetric conformations of PKSs.
Databáze: OpenAIRE
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