Article
- The EMBO Journal (2004) 23, 2931 - 2941
- doi:10.1038/sj.emboj.7600320
Published online: 22 July 2004
Subject Categories:
A hydrocarbon ruler measures palmitate in the enzymatic acylation of endotoxin
Victoria E Ahn1,a, Eileen I Lo2,a, Christian K Engel3,b, Lu Chen3, Peter M Hwang2, Lewis E Kay2,4,5, Russell E Bishop2,6 and Gilbert G Privé1,2,3
- Department of Medical Biophysics, University of Toronto, Canada
- Department of Biochemistry, University of Toronto, Canada
- Division of Molecular and Structural Biology, Ontario Cancer Institute, Canada
- Department of Medical Genetics and Microbiology, University of Toronto, Canada
- Department of Chemistry, University of Toronto, Canada
- Department of Laboratory Medicine and Pathobiology, University of Toronto, Canada
Correspondence to:
Russell E Bishop, 6213 Medical Sciences Building, 1 King's College Circle, Toronto, Ontario, Canada M5S 1A8. E-mail: russell.bishop@utoronto.ca
Gilbert G Privé, Department of Medical Biophysics, University of Toronto, 610 University Avenue, Toronto, Ontario, Canada M5G 2M9. Tel.: +1 416 946 2971; Fax: +1 416 946 6529; E-mail: prive@uhnres.utoronto.ca
aThese authors contributed equally to this work
bPresent address: Aventis Pharma, 65926 Frankfurt, Germany
Received 4 May 2004; Accepted 18 June 2004
Abstract
The 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 Å crystal structure of PagP, an eight-stranded 
-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 -barrel axis is tilted by approximately 25°. 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.
Keywords:
- crystal structure,
- endotoxin,
- lipid A,
- phospholipids,
- signal transduction
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated
NEWS AND VIEWS
Engineering protease specificity made simple, but not simpler
Nature Chemical Biology News and Views (01 May 2008)
Engineering protease specificity made simple, but not simpler
Nature Chemical Biology News and Views (01 May 2008)
RESEARCH
Transfer of palmitate from phospholipids to lipid A in outer membranes of Gram-negative bacteria
The EMBO Journal Article (02 Oct 2000)
Structure and biochemical analysis of a secretin pilot protein
The EMBO Journal Article (23 Mar 2005)
