Structure-Based Design of a Br Halogen Bond at the Complex Interface of the Human Placental HtrA1 PDZ Domain with Its Heptapeptide Ligand.

The shock-induced serine protease HtrA1 is a potential regulator of human placenta development during pregnancy. The protein contains a functional PDZ domain that has been solved in complex with a phage display-derived heptapeptide: Asp-6 Ser-5 Arg-4 Ile-3 Trp-2 Trp-1 Val0 . In this study, a rationally designed halogen bond was introduced to the domain-peptide complex based on its NMR structure in solution. We computationally compared the stabilization energies and hindrance effects due to the presence of different halogens X (X = F, Cl, Br, or I), using a hybrid quantum mechanics/molecular mechanics (QM/MM) approach, and found that the Br atom could considerably promote the peptide binding free energy (ΔΔG = -5.2 kcal/mol). Fluorescence assays confirmed that the peptide affinity to the HtrA1 PDZ domain was improved by approximately sevenfold upon bromination. Structural analysis identified a geometrically perfect halogen bond between the Br atom of the peptide Trp-1 residue and the carbonyl O atom of the HtrA1 Ile385 residue, with a bond length and an interaction energy of d = 3.20 Å and ΔE = -3.7 kcal/mol, respectively.

Serological reports of human infections of H7 and H9 avian influenza viruses in northern China.

BACKGROUND: H7 and H9 subtype avian influenza viruses pose a similar threat to humans as H5 virus. OBJECTIVES: This study aims to identify the potential existence of H7 and H9 avian influenza infections in farmers and in poultry workers in northern China regions with highly pathogenic avian influenza (HPAI) H5N1 outbreaks. STUDY DESIGN: Sera were collected from farmers in Xinjiang Uygur autonomous region and Liaoning province and poultry workers in Shandong province. Sera from healthy residents in Shanxi province were used as the controls. H7 and H9 virus infections were examined by hemagglutination inhibition (HI) assay using horse erythrocytes. The titer equal to or greater than 1:160 was considered positive. RESULTS: A total of 583 sera collected from farmers in Xinjiang were tested, and 10 (1.7%) were positive for H9 virus infection. Out of 200 sera collected from Liaoning, two (1.0%) were infected by H9 virus. No H7 virus infection was detected in the above serum samples. Neither H7 nor H9 virus infection was identified in 277 poultry workers of Shandong and in 407 residents of Shanxi. CONCLUSIONS: Although H9 virus infection was limited in farmers from Xinjiang and Liaoning, a public health alert is needed as novel pandemic influenza strains may develop unnoticed given the presence of subclinical infections, and the possibility of re-assortment with prevailing H5N1 virus in these regions.