In:
Proteins: Structure, Function, and Bioinformatics, Wiley, Vol. 88, No. 1 ( 2020-01), p. 47-56
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0887-3585
,
1097-0134
Language:
English
Publisher:
Wiley
Publication Date:
2020
detail.hit.zdb_id:
1475032-6
SSG:
12
