Linked Life Data

17375935

Source:http://linkedlifedata.com/resource/pubmed/id/17375935

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2007-4-10
pubmed:abstractText
The structural basis of lipid acyl-chain selection by membrane-intrinsic enzymes is poorly understood because most integral membrane enzymes of lipid metabolism have proven refractory to structure determination; however, robust enzymes from the outer membranes of gram-negative bacteria are now providing a first glimpse at the underlying mechanisms. The methylene unit resolution of the phospholipid:lipid A palmitoyltransferase PagP is determined by the hydrocarbon ruler, a 16-carbon saturated acyl-chain-binding pocket buried within the transmembrane beta-barrel structure. Substitution of Gly88 lining the floor of the hydrocarbon ruler with Ala or Met makes the enzyme select specifically 15- or 12-carbon saturated acyl chains, respectively, indicating that hydrocarbon ruler depth determines acyl-chain selection. However, the Gly88Cys PagP resolution does not diminish linearly because it selects both 14- and 15-carbon saturated acyl chains. We discovered that an exciton, emanating from a buried Tyr26-Trp66 phenol-indole interaction, is extinguished by a local structural perturbation arising from the proximal Gly88Cys PagP sulfhydryl group. Site-specific S-methylation of the single Cys afforded Gly88Cys-S-methyl PagP, which reasserted both the exciton and methylene unit resolution by specifically selecting 13-carbon saturated acyl chains for transfer to lipid A. Unlike the other Gly88 substitutions, the Cys sulfhydryl group recedes from the hydrocarbon ruler floor and locally perturbs the subjacent Tyr26 and Trp66 aromatic rings. The resulting hydrocarbon ruler expansion thus occurs at the exciton's expense and accommodates an extra methylene unit in the selected acyl chain. The hydrocarbon ruler-exciton juxtaposition endows PagP with a molecular gauge for probing the structural basis of lipid acyl-chain selection in a membrane-intrinsic environment.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-2960
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4565-79
pubmed:meshHeading
pubmed-meshheading:17375935-Acyltransferases, pubmed-meshheading:17375935-Amino Acid Substitution, pubmed-meshheading:17375935-Bacterial Outer Membrane Proteins, pubmed-meshheading:17375935-Binding Sites, pubmed-meshheading:17375935-Calorimetry, Differential Scanning, pubmed-meshheading:17375935-Circular Dichroism, pubmed-meshheading:17375935-Cysteine, pubmed-meshheading:17375935-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:17375935-Escherichia coli Proteins, pubmed-meshheading:17375935-Glycine, pubmed-meshheading:17375935-Lipid A, pubmed-meshheading:17375935-Methylation, pubmed-meshheading:17375935-Models, Molecular, pubmed-meshheading:17375935-Phospholipids, pubmed-meshheading:17375935-Protein Folding, pubmed-meshheading:17375935-Protein Structure, Secondary, pubmed-meshheading:17375935-Protein Structure, Tertiary, pubmed-meshheading:17375935-Spectrometry, Mass, Electrospray Ionization, pubmed-meshheading:17375935-Substrate Specificity, pubmed-meshheading:17375935-Thermodynamics
pubmed:year
2007
pubmed:articleTitle
Gauging a hydrocarbon ruler by an intrinsic exciton probe.
pubmed:affiliation
Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada M5S 1A8.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't