1thq
From Proteopedia
Crystal Structure of Outer Membrane Enzyme PagP
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 PubMedThe ability of enzymes to distinguish between fatty acyl groups can involve molecular measuring devices termed hydrocarbon rulers, but the molecular basis for acyl-chain recognition in any membrane-bound enzyme remains to be defined. PagP is an outer membrane acyltransferase that helps pathogenic bacteria to evade the host immune response by transferring a palmitate chain from a phospholipid to lipid A (endotoxin). PagP can distinguish lipid acyl chains that differ by a single methylene unit, indicating that the enzyme possesses a remarkably precise hydrocarbon ruler. We present the 1.9 A crystal structure of PagP, an eight-stranded beta-barrel with an unexpected interior hydrophobic pocket that is occupied by a single detergent molecule. The buried detergent is oriented normal to the presumed plane of the membrane, whereas the PagP beta-barrel axis is tilted by approximately 25 degrees. Acyl group specificity is modulated by mutation of Gly88 lining the bottom of the hydrophobic pocket, thus confirming the hydrocarbon ruler mechanism for palmitate recognition. A striking structural similarity between PagP and the lipocalins suggests an evolutionary link between these proteins. A hydrocarbon ruler measures palmitate in the enzymatic acylation of endotoxin.,Ahn VE, Lo EI, Engel CK, Chen L, Hwang PM, Kay LE, Bishop RE, Prive GG EMBO J. 2004 Aug 4;23(15):2931-41. Epub 2004 Jul 22. PMID:15272304[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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