title: LpxI structures reveal how a lipid A precursor is synthesized.
abstract: Enzymes in lipid metabolism acquire and deliver hydrophobic substrates and products from within lipid bilayers. The structure at 2.55 Å of one isozyme of a constitutive enzyme in lipid A biosynthesis, LpxI from Caulobacter crescentus, has a novel fold. Two domains close around a completely sequestered substrate, UDP-2,3-diacylglucosamine, and open to release products either to the neighboring enzyme in a putative multienzyme complex or to the bilayer. Mutation analysis identifies Asp225 as key to Mg(2+)-catalyzed diphosphate hydrolysis. These structures provide snapshots of the enzymatic synthesis of a critical lipid A precursor.
authors.affiliation: Department of Biochemistry and Biophysics, The University of California San Francisco, San Francisco, California, USA. metzger@msg.ucsf.edu
authors.forename: Louis E
authors.initials: LE
authors.lastname: Metzger
authors.forename: John K
authors.initials: JK
authors.lastname: Lee
authors.forename: Janet S
authors.initials: JS
authors.lastname: Finer-Moore
authors.forename: Christian R H
authors.initials: CR
authors.lastname: Raetz
authors.forename: Robert M
authors.initials: RM
authors.lastname: Stroud
mesh_terms: D000595:Amino Acid Sequence; D016935:Caulobacter crescentus / Q000201:enzymology*; D003460:Crystallization; D004252:DNA Mutational Analysis; D006017:Glycolipids / Q000378:metabolism; D007527:Isoenzymes / Q000737:chemistry; D008050:Lipid A / Q000096:biosynthesis*; D013058:Mass Spectrometry; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D011487:Protein Conformation; D017510:Protein Folding; D011755:Pyrophosphatases / Q000737:chemistry* / Q000235:genetics; D014461:Ultracentrifugation
chemical_list: D006017:Glycolipids; D007527:Isoenzymes; D008050:Lipid A; C044283:lipid X; D011755:Pyrophosphatases; C464799:UDP-2,3-diacylglucosamine pyrophosphatase