6B9I

The crystal structure of the Staphylococcus aureus Fatty acid Kinase (Fak) B1 protein loaded with 14-Methylhexadecanoic Acid (Anteiso C17:0) to 1.93 Angstrom resolution

Summary for 6B9I

• Entry DOI: 10.2210/pdb6b9i/pdb
• Related: 5UTO 5UXY 5V85 5WOO 6ALW
• Descriptor: Fatty acid Kinase (Fak) B1, (14S)-14-methylhexadecanoic acid, GLYCEROL, ... (5 entities in total)
• Functional Keywords: staphylococcus aureus, fakb1, 12-methyl 14-methylhexadecanoic, anteiso c17:0, transferase
• Biological source: Staphylococcus aureus
• Total number of polymer chains: 2
• Total formula weight: 65802.93

Authors

Cuypers, M.G.,Ericson, M.,Subramanian, C.,White, S.W.,Rock, C.O. (deposition date: 2017-10-10, release date: 2018-10-10, Last modification date: 2023-10-04)

Primary citation

Cuypers, M.G.,Subramanian, C.,Gullett, J.M.,Frank, M.W.,White, S.W.,Rock, C.O.
Acyl-chain selectivity and physiological roles ofStaphylococcus aureusfatty acid-binding proteins.
J. Biol. Chem., 294:38-49, 2019

PubMed Abstract: Fatty acid (FA) kinase produces acyl-phosphate for the synthesis of membrane phospholipids in Gram-positive bacterial pathogens. FA kinase consists of a kinase protein (FakA) that phosphorylates an FA substrate bound to a second module, an FA-binding protein (FakB). expresses two distinct, but related, FakBs with different FA selectivities. Here, we report the structures of FakB1 bound to four saturated FAs at 1.6-1.93 Å resolution. We observed that the different FA structures are accommodated within a slightly curved hydrophobic cavity whose length is governed by the conformation of an isoleucine side chain at the end of the tunnel. The hydrophobic tunnel in FakB1 prevents the binding of -unsaturated FAs, which are instead accommodated by the kinked tunnel within the FakB2 protein. The differences in the FakB interiors are not propagated to the proteins' surfaces, preserving the protein-protein interactions with their three common partners, FakA, PlsX, and PlsY. Using cellular thermal shift analyses, we found that FakB1 binds FA , whereas a significant proportion of FakB2 does not. Incorporation of exogenous FA into phospholipid in Δ and Δ knockout strains revealed that FakB1 does not efficiently activate unsaturated FAs. FakB2 preferred unsaturated FAs, but also allowed the incorporation of saturated FAs. These results are consistent with a model in which FakB1 primarily functions in the recycling of the saturated FAs produced by metabolism, whereas FakB2 activates host-derived oleate, which does not produce but is abundant at infection sites.

PubMed: 30429218
DOI: 10.1074/jbc.RA118.006160

Experimental method

X-RAY DIFFRACTION (1.93 Å)