Structure of the N-terminal region of Haemophilus influenzae H10017: implications for function.
Haemophilus influenzae is a gram-negative pathogen that causes infections ranging from asymptomatic colonization of the human upper respiratory tract to serious invasive diseases such as meningitis. Although the genome of Haemophilus influenzae has been completely sequenced, the structure and function of many of these proteins are unknown. H10017 is one of these uncharacterized proteins. Here we describe the three-dimensional solution structure of the N-terminal portion of H10017 as determined by NMR spectroscopy. The structure consists of a five-stranded antiparallel beta-sheet and two short alpha-helices. It is similar to the C-terminal domain of Diphtheria toxin repressor (DtxR). The C-terminal portion of H10017 has an amino acid sequence that closely resembles pyruvate formate-lyase--an enzyme that converts pyruvate and CoA into acetyl-CoA and formate by a radical mechanism. Based on structural and sequence comparisons, we propose that the C-terminus of H10017 functions as an enzyme with a glycyl radical mechanism, while the N-terminus participates in protein/protein interactions involving an activase (iron-sulfur protein) and/or the substrate.
Yu
L
L
Pharmaceutical Discovery Division, Abbott Laboratories, Abbott Park, IL 60064-6098, USA. Liping.Yu@abbott.com
Mack
J
J
Hajduk
P
P
Fesik
S W
SW
D000123:Acetyltransferases / Q000235:genetics; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry; D006193:Haemophilus influenzae / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D017386:Sequence Homology, Amino Acid
D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; C075586:DtxR protein, Corynebacterium diphtheriae; D000123:Acetyltransferases; C022560:formate C-acetyltransferase