文献类型：期刊文献

英文题名：Structure binding relationship of human surfactant protein D and various lipopolysaccharide inner core structures

作者：Reinhardt, Anika[1,2];Wehle, Marko[4];Geissner, Andreas[1,2];Crouch, Erika C.[3];Kang, Yu[4,5];Yang, You[1,7];Anish, Chakkumkal[1,6];Santer, Mark[4];Seeberger, Peter H.[1,2]

机构：[1]Max Planck Inst Colloids & Interfaces, Dept Biomol Syst, D-14476 Potsdam, Germany;[2]Free Univ Berlin, Inst Chem & Biochem, Arnimallee 22, D-14195 Berlin, Germany;[3]Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA;[4]Max Planck Inst Colloids & Interfaces, Dept Theory & Biosyst, D-14476 Potsdam, Germany;[5]Zhejiang Univ, Coll Pharmaceut Sci, Hangzhou 310058, Zhejiang, Peoples R China;[6]Johnson & Johnson, Janssen Pharmaceut, Bacterial Vaccine Discovery Team, Biosci Pk Leiden,Zernikedreef 9, NL-2333 CK Leiden, Netherlands;[7]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, 130 Meilong Rd, Shanghai 200237, Peoples R China

年份：2016

卷号：195

期号：3

起止页码：387

外文期刊名：JOURNAL OF STRUCTURAL BIOLOGY

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000381777700014)】；

基金：We thank the Max Planck Society and the Korber Foundation (Korber Prize to P.H.S.) for generous financial support and the Studienstiftung des Deutschen Volkes for a graduate fellowship (A.R.). C.A. acknowledges support by German Federal Ministry of Education and Research (grant 0315447). We acknowledge Mr. Felix Broecker and Dr. Sebastian Goetze for valuable discussions and careful review of the manuscript.

语种：英文

外文关键词：Surfactant protein D; D324N+D325N+R343K mutant; Carbohydrate recognition domain; Lipopolysaccharide inner core structure; Gram-negative bacteria; Glycan array; Surface plasmon resonance; Molecular docking; Molecular dynamics simulations; Synthetic glycans; Glycan binding affinity

摘要：As a major player of the innate immune system, surfactant protein D (SP-D) recognizes and promotes elimination of various pathogens such as Gram-negative bacteria. SP-D binds to L-glycero-D-mannoheptose (Hep), a constituent of the partially conserved lipopolysaccharide (LPS) inner core of many Gram-negative bacteria. Binding and affinity of trimeric human SP-D to Hep in distinct LPS inner core glycans differing in linkages and adjacent residues was elucidated using glycan array and surface plasmon resonance measurements that were compared to in silico interaction studies. The combination of in vitro assays using defined glycans and molecular docking and dynamic simulation approaches provides insights into the interaction of trimeric SP-D with those glycan ligands. Trimeric SP-D wildtype recognized larger LPS inner core oligosaccharides with slightly enhanced affinity than smaller compounds suggesting the involvement of stabilizing secondary interactions. A trimeric human SP-D mutant D324N + D325N + R343K resembling rat SP-D bound to various LPS inner core structures in a similar pattern as observed for the wildtype but with higher affinity. The selective mutation of SP-D promotes targeting of LPS inner core oligosaccharides on Gram-negative bacteria to develop novel therapeutic agents. (C) 2016 Published by Elsevier Inc.