Structural studies of Salmonella typhimurium ArnB (PmrH) aminotransferase: a 4-amino-4-deoxy-L-arabinose lipopolysaccharide-modifying enzyme.
Lipid A modification with 4-amino-4-deoxy-L-arabinose confers on certain pathogenic bacteria, such as Salmonella, resistance to cationic antimicrobial peptides, including those derived from the innate immune system. ArnB catalysis of amino group transfer from glutamic acid to the 4"-position of a UDP-linked ketopyranose molecule to form UDP-4-amino-4-deoxy-L-arabinose represents a key step in the lipid A modification pathway. Structural and functional studies of the ArnB aminotransferase were undertaken by combining X-ray crystallography with biochemical analyses. High-resolution crystal structures were solved for two native forms and one covalently inhibited form of S. typhimurium ArnB. These structures permitted identification of key residues involved in substrate binding and catalysis, including a rarely observed nonprolyl cis peptide bond in the active site.
Noland
Brian W
BW
Structural Genomix, San Diego, CA 92121, USA. brian.noland@stromix.com
Newman
Janet M
JM
Hendle
Jörg
J
Badger
John
J
Christopher
Jon A
JA
Tresser
Jason
J
Buchanan
Michelle D
MD
Wright
Tobi A
TA
Rutter
Marc E
ME
Sanderson
Wendy E
WE
Müller-Dieckmann
Hans Joachim
HJ
Gajiwala
Ketan S
KS
Buchanan
Sean G
SG
D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D003523:Cycloserine / Q000737:chemistry; D004926:Escherichia coli / Q000378:metabolism; D008070:Lipopolysaccharides / Q000378:metabolism; D013058:Mass Spectrometry; D008956:Models, Chemical; D008958:Models, Molecular; D008969:Molecular Sequence Data; D017510:Protein Folding; D017433:Protein Structure, Secondary; D011733:Pyridoxamine / Q000031:analogs & derivatives* / Q000737:chemistry; D012486:Salmonella typhimurium / Q000201:enzymology*; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D000637:Transaminases / Q000737:chemistry*
D008070:Lipopolysaccharides; D011733:Pyridoxamine; D003523:Cycloserine; D000637:Transaminases; C010627:pyridoxamine phosphate