title: Structure determination of LpxA from the lipopolysaccharide-synthesis pathway of Acinetobacter baumannii.
abstract: Acinetobacter baumannii is a Gram-negative pathogenic bacterium which is resistant to most currently available antibiotics and that poses a significant health threat to hospital patients. LpxA is a key enzyme in the biosynthetic pathway of the lipopolysaccharides that are components of the bacterial outer membrane. It is a potential target for antibacterial agents that might be used to fight A. baumannii infections. This paper describes the structure determination of the apo form of LpxA in space groups P2(1)2(1)2(1) and P6(3). These crystal forms contained three and one protein molecules in the asymmetric unit and diffracted to 1.8 and 1.4 Å resolution, respectively. A comparison of the conformations of the independent protein monomers within and between the two crystal asymmetric units revealed very little structural variation across this set of structures. In the P6(3) crystal form the enzymatic site is exposed and is available for the introduction of small molecules of the type used in fragment-based drug discovery and structure-based lead optimization.
authors.affiliation: Zenobia Therapeutics Inc., 505 Coast Boulevard South, Suite 111, La Jolla, CA 92037, USA. john@zenobiatherapeutics.com
authors.forename: John
authors.initials: J
authors.lastname: Badger
authors.forename: Barbara
authors.initials: B
authors.lastname: Chie-Leon
authors.forename: Cheyenne
authors.initials: C
authors.lastname: Logan
authors.forename: Vandana
authors.initials: V
authors.lastname: Sridhar
authors.forename: Banumathi
authors.initials: B
authors.lastname: Sankaran
authors.forename: Peter H
authors.initials: PH
authors.lastname: Zwart
authors.forename: Vicki
authors.initials: V
authors.lastname: Nienaber
mesh_terms: D040981:Acinetobacter baumannii / Q000201:enzymology* / Q000378:metabolism; D000217:Acyltransferases / Q000737:chemistry* / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000737:chemistry* / Q000378:metabolism; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D018360:Crystallography, X-Ray; D008958:Models, Molecular; D011487:Protein Conformation
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D000217:Acyltransferases