3gp6
From Proteopedia
Crystal structure of PagP in SDS/MPD
Structural highlights
Function[PAGP_ECOLI] PagP is required both for biosynthesis of hepta-acylated lipid A species containing palmitate and for resistance to cationic antimicrobial peptides (CAMPs). It catalyzes the transfer of a palmitate chain (16:0) from the sn-1 position of a glycerophospholipid to the free hydroxyl group of the (R)-3-hydroxymyristate chain at position 2 of lipid A (endotoxin). Modifications of lipid A with a palmitate chain allow to evade host immune defenses by resisting antimicrobial peptides and attenuating the inflammatory response to infection triggered by lipopolysaccharide through the Toll-like receptor 4 (TLR4) signal transduction pathway. Phosphatidylglycerol (PtdGro), phosphatidylethanolamine (PtdEtn), phosphatidylserine (PtdSer) and phosphatidic acid (Ptd-OH) are all effective acyl donors.[1] Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMedEnzymatic reactions involving bilayer lipids occur in an environment with strict physical and topological constraints. The integral membrane enzyme PagP transfers a palmitoyl group from a phospholipid to lipid A in order to assist Escherichia coli in evading host immune defenses during infection. PagP measures the palmitoyl group with an internal hydrocarbon ruler that is formed in the interior of the eight-stranded antiparallel beta barrel. The access and egress of the palmitoyl group is thought to take a lateral route from the bilayer phase to the barrel interior. Molecular dynamics, mutagenesis, and a 1.4 A crystal structure of PagP in an SDS / 2-methyl-2,4-pentanediol (MPD) cosolvent system reveal that phospholipid access occurs at the crenel present between strands F and G of PagP. In this way, the phospholipid head group can remain exposed to the cell exterior while the lipid acyl chain remains in a predominantly hydrophobic environment as it translocates to the protein interior. PagP crystallized from SDS/cosolvent reveals the route for phospholipid access to the hydrocarbon ruler.,Cuesta-Seijo JA, Neale C, Khan MA, Moktar J, Tran CD, Bishop RE, Pomes R, Prive GG Structure. 2010 Sep 8;18(9):1210-9. PMID:20826347[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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Categories: Ecoli | Cuesta-Seijo, J A | Prive, G G | Beta-barrel | Mpd | Outer membrane enzyme | Pagp | Palmitoyltransferase | Sd | Transferase
