Structural characterization of β‐ketoacyl ACP synthase I bound to platencin and fragment screening molecules at two substrate binding sites
In: Proteins Structure Function and Bioinformatics, Jg. 88 (2020), Heft 1
Online
academicJournal
- 47 - 56
The bacterial fatty acid pathway is essential for membrane synthesis and a range of other metabolic and cellular functions. The β-ketoacyl-ACP synthases carry out the initial elongation reaction of this pathway, utilizing acetyl-CoA as a primer to elongate malonyl-ACP by two carbons, and subsequent elongation of the fatty acyl-ACP substrate by two carbons. Here we describe the structures of the β-ketoacyl-ACP synthase I from Brucella melitensis in complex with platencin, 7-hydroxycoumarin, and (5-thiophen-2-ylisoxazol-3-yl)methanol. The enzyme is a dimer and based on structural and sequence conservation, harbors the same active site configuration as other β-ketoacyl-ACP synthases. The platencin binding site overlaps with the fatty acyl compound supplied by ACP, while 7-hydroxyl-coumarin and (5-thiophen-2-ylisoxazol-3-yl)methanol bind at the secondary fatty acyl binding site. These high-resolution structures, ranging between 1.25 and 1.70 å resolution, provide a basis for in silico inhibitor screening and optimization, and can aid in rational drug design by revealing the high-resolution binding interfaces of molecules at the malonyl-ACP and acyl-ACP active sites.
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Structural characterization of β‐ketoacyl ACP synthase I bound to platencin and fragment screening molecules at two substrate binding sites
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Autor/in / Beteiligte Person: | Patterson, Edward I ; Nanson, Jeffrey D ; Abendroth, Jan ; Bryan, Cassie ; Sankaran, Banumathi ; Myler, Peter J ; Forwood, Jade K |
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Zeitschrift: | Proteins Structure Function and Bioinformatics, Jg. 88 (2020), Heft 1 |
Veröffentlichung: | eScholarship, University of California, 2020 |
Medientyp: | academicJournal |
Umfang: | 47 - 56 |
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