8GHI

Crystal structure of Staphylococcus aureus Lysophosphatidylglycerol phospholipase D

8GHI の概要

• エントリーDOI: 10.2210/pdb8ghi/pdb
• 分子名称: Glycerophosphodiester phosphodiesterase, DIHYDROGENPHOSPHATE ION, GLYCEROL, ... (4 entities in total)
• 機能のキーワード: glycerophosphodiester phosphodiesterase (gdpd), hydrolase, phospholipase d, lysophosphatidic acid, lysophosphatidylglycerol
• 由来する生物種: Staphylococcus aureus
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 33665.07

構造登録者

Rock, C.O.,Yun, M. (登録日: 2023-03-10, 公開日: 2023-11-01)

主引用文献

Subramanian, C.,Yun, M.K.,Frank, M.M.,Rock, C.O.
Lysophosphatidylglycerol (LPG) phospholipase D maintains membrane homeostasis in Staphylococcus aureus by converting LPG to lysophosphatidic acid.
J.Biol.Chem., 299:104863-104863, 2023

PubMed Abstract: Lysophospholipids are deacylated derivatives of their bilayer forming phospholipid counterparts that are present at low concentrations in cells. Phosphatidylglycerol (PG) is the principal membrane phospholipid in Staphylococcus aureus and lysophosphatidylglycerol (LPG) is detected in low abundance. Here, we used a mass spectrometry screen to identify locus SAUSA300_1020 as the gene responsible for maintaining low concentrations of 1-acyl-LPG in S. aureus. The SAUSA300_1020 gene encodes a protein with a predicted amino terminal transmembrane α-helix attached to a globular glycerophosphodiester phosphodiesterase (GDPD) domain. We determined that the purified protein lacking the hydrophobic helix (LpgDΔN) possesses cation-dependent lysophosphatidylglycerol phospholipase D activity that generates both lysophosphatidic acid (LPA) and cyclic-LPA products and hydrolyzes cyclic-LPA to LPA. Mn was the highest affinity cation and stabilized LpgDΔN to thermal denaturation. LpgDΔN was not specific for the phospholipid headgroup and degraded 1-acyl-LPG, but not 2-acyl-LPG. Furthermore, a 2.1 Å crystal structure shows that LpgDΔN adopts the GDPD variation of the TIM barrel architecture except for the length and positioning of helix α6 and sheet β7. These alterations create a hydrophobic diffusion path for LPG to access the active site. The LpgD active site has the canonical GDPD metal binding and catalytic residues, and our biochemical characterization of site-directed mutants support a two-step mechanism involving a cyclic-LPA intermediate. Thus, the physiological function of LpgD in S. aureus is to convert LPG to LPA, which is re-cycled into the PG biosynthetic pathway at the LPA acyltransferase step to maintain membrane PG molecular species homeostasis.

PubMed: 37236358
DOI: 10.1016/j.jbc.2023.104863

実験手法

X-RAY DIFFRACTION (2.4 Å)