NDLI: Probing the interactions of an acyl carrier protein domain from the 6-deoxyerythronolide B synthase.

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Probing the interactions of an acyl carrier protein domain from the 6-deoxyerythronolide B synthase.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Capone, Stefania Seebach, Dieter Khosla, Chaitan Kapur, Shiven Cane, David E. Charkoudian, Louise K. Togni, Antonio Liu, Corey W.
Description	Country affiliation: United States Author Affiliation: Charkoudian LK ( Department of Chemistry, Stanford University, Stanford, California 94305, USA.)
Abstract	The assembly-line architecture of polyketide synthases (PKSs) provides an opportunity to rationally reprogram polyketide biosynthetic pathways to produce novel antibiotics. A fundamental challenge toward this goal is to identify the factors that control the unidirectional channeling of reactive biosynthetic intermediates through these enzymatic assembly lines. Within the catalytic cycle of every PKS module, the acyl carrier protein (ACP) first collaborates with the ketosynthase (KS) domain of the paired subunit in its own homodimeric module so as to elongate the growing polyketide chain and then with the KS domain of the next module to translocate the newly elongated polyketide chain. Using NMR spectroscopy, we investigated the features of a structurally characterized ACP domain of the 6-deoxyerythronolide B synthase that contribute to its association with its KS translocation partner. Not only were we able to visualize selective protein-protein interactions between the two partners, but also we detected a significant influence of the acyl chain substrate on this interaction. A novel reagent, CF3-S-ACP, was developed as a ¹9F NMR spectroscopic probe of protein-protein interactions. The implications of our findings for understanding intermodular chain translocation are discussed.
ISSN	09618368
e-ISSN	1469896X
DOI	10.1002/pro.652
Journal	Protein Science
Issue Number	7
Volume Number	20
Language	English
Publisher	Wiley-Blackwell (on behalf of The Protein Society)
Publisher Date	2011-07-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Acyl Carrier Protein Metabolism Nuclear Magnetic Resonance, Biomolecular Polyketide Synthases Chemistry Protein Interaction Mapping Saccharopolyspora Enzymology Acyltransferases Models, Molecular Protein Structure, Tertiary Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't Discipline Biochemistry
Content Type	Text
Resource Type	Article
Subject	Medicine Molecular Biology Biochemistry

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Probing the interactions of an acyl carrier protein domain from the 6-deoxyerythronolide B synthase

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