3U0F

The structure of Beta-ketoacyl synthase from Brucella melitensis bound to the fragment 7-hydroxycoumarin

Summary for 3U0F

• Entry DOI: 10.2210/pdb3u0f/pdb
• Related: 3LRF 3MQD 3U0E
• Descriptor: Beta-ketoacyl synthase, CHLORIDE ION, SODIUM ION, ... (6 entities in total)
• Functional Keywords: seattle structural genomics center for infectious disease, ssgcid, beta-ketoacyl synthase, transferase
• Biological source: Brucella melitensis biovar Abortus
• Total number of polymer chains: 1
• Total formula weight: 43972.19

Authors

Seattle Structural Genomics Center for Infectious Disease (SSGCID) (deposition date: 2011-09-28, release date: 2011-10-12, Last modification date: 2025-10-22)

Primary citation

Patterson, E.I.,Nanson, J.D.,Abendroth, J.,Bryan, C.,Sankaran, B.,Myler, P.J.,Forwood, J.K.
Structural characterization of beta-ketoacyl ACP synthase I bound to platencin and fragment screening molecules at two substrate binding sites.
Proteins, 88:47-56, 2020

PubMed 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.

PubMed: 31237717
DOI: 10.1002/prot.25765

Experimental method

X-RAY DIFFRACTION (1.25 Å)