Solution structure of the highly acidic protein HI1450 from Haemophilus influenzae, a putative double-stranded DNA mimic.
The solution structure of the acidic protein HI1450 from Haemophilus influenzae has been determined by NMR spectroscopy. HI1450 has homologues in ten other bacterial species including Escherichia coli, Vibrio cholerae, and Yersinia pestis but there are no functional assignments for any members of the family. Thirty-one of the amino acids in this 107-residue protein are aspartates or glutamates, contributing to an unusually low pI of 3.72. The secondary structure elements are arranged in an alpha-alpha-beta-beta-beta-beta order with the two alpha helices packed against the same side of an anti-parallel four-stranded beta meander. Two large loops, one between beta1 and beta2 and the other between beta2 and beta3 bend almost perpendicularly across the beta-strands in opposite directions on the non-helical side of the beta-sheet to form a conserved hydrophobic cavity. The HI1450 structure has some similarities to the structure of the double-stranded DNA (dsDNA) mimic uracil DNA glycosylase inhibitor (Ugi) including the distribution of surface charges and the position of the hydrophobic cavity. Based on these similarities, as well as having a comparable molecular surface to dsDNA, we propose that HI1450 may function as a dsDNA mimic in order to inhibit or regulate an as yet unidentified dsDNA binding protein.
Parsons
Lisa M
LM
Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, Rockville, Maryland 20850, USA.
Yeh
Deok Cheon
DC
Orban
John
J
D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000378:metabolism; D004247:DNA / Q000737:chemistry*; D006193:Haemophilus influenzae / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D012996:Solutions
D001426:Bacterial Proteins; D012996:Solutions; D004247:DNA