7DRJ

Crystal structure of phosphatidylglycerol phosphate synthase in complex with phosphatidylglycerol phosphate

Summary for 7DRJ

• Entry DOI: 10.2210/pdb7drj/pdb
• Descriptor: CDP-diacylglycerol--glycerol-3-phosphate 3-phosphatidyltransferase, [(2R)-2-hexadecanoyloxy-3-[oxidanyl-[(2S)-2-oxidanyl-3-phosphonooxy-propoxy]phosphoryl]oxy-propyl] (Z)-octadec-9-enoate, 1,4-BUTANEDIOL, ... (7 entities in total)
• Functional Keywords: product complex, phospholipid synthase, staphylococcus aureus, transferase., transferase
• Biological source: Staphylococcus aureus (strain N315)
• Total number of polymer chains: 2
• Total formula weight: 51543.11

Authors

Yang, B.W.,Liu, Z.F. (deposition date: 2020-12-28, release date: 2021-12-08, Last modification date: 2024-05-29)

Primary citation

Yang, B.,Yao, H.,Li, D.,Liu, Z.
The phosphatidylglycerol phosphate synthase PgsA utilizes a trifurcated amphipathic cavity for catalysis at the membrane-cytosol interface.
Curr Res Struct Biol, 3:312-323, 2021

PubMed Abstract: Phosphatidylglycerol is a crucial phospholipid found ubiquitously in biological membranes of prokaryotic and eukaryotic cells. The phosphatidylglycerol phosphate (PGP) synthase (PgsA), a membrane-embedded enzyme, catalyzes the primary reaction of phosphatidylglycerol biosynthesis. Mutations in frequently correlate with daptomycin resistance in and other prevalent infectious pathogens. Here we report the crystal structures of PgsA (PgsA) captured at two distinct states of the catalytic process, with lipid substrate (cytidine diphosphate-diacylglycerol, CDP-DAG) or product (PGP) bound to the active site within a trifurcated amphipathic cavity. The hydrophilic head groups of CDP-DAG and PGP occupy two different pockets in the cavity, inducing local conformational changes. An elongated membrane-exposed surface groove accommodates the fatty acyl chains of CDP-DAG/PGP and opens a lateral portal for lipid entry/release. Remarkably, the daptomycin resistance-related mutations mostly cluster around the active site, causing reduction of enzymatic activity. Our results provide detailed mechanistic insights into the dynamic catalytic process of PgsA and structural frameworks beneficial for development of antimicrobial agents targeting PgsA from pathogenic bacteria.

PubMed: 34901881
DOI: 10.1016/j.crstbi.2021.11.005

Experimental method

X-RAY DIFFRACTION (2.5 Å)