Solution structure of the highly acidic protein HI1450 from Haemophilus influenzae, a putative double‐stranded DNA mimic

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Abstract
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 α‐α‐β‐β‐β‐β order with the two alpha helices packed against the same side of an anti‐parallel four‐stranded beta meander. Two large loops, one between β1 and β2 and the other between β2 and β3 bend almost perpendicularly across the β‐strands in opposite directions on the non‐helical side of the β‐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. Proteins 2004;54:000–000.