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Structure-function of the TNF receptor-like cysteine-rich domain of osteoprotegerin

Authors
 Joon Shin  ;  Young-Mee Kim  ;  Song-Zhe Li  ;  Sung-Kil Lim  ;  Weontae Lee 
Citation
 MOLECULES AND CELLS, Vol.25(3) : 352-357, 2008 
Journal Title
 MOLECULES AND CELLS 
ISSN
 1016-8478 
Issue Date
2008
MeSH
Animals ; Cells, Cultured ; Cysteine/analysis ; Macrophage Colony-Stimulating Factor/antagonists & inhibitors ; Mice ; Nuclear Magnetic Resonance, Biomolecular ; Osteoclasts/cytology ; Osteoclasts/drug effects* ; Osteoprotegerin/chemistry* ; Peptides/chemistry* ; Peptides/pharmacology* ; Protein Structure, Tertiary ; RANK Ligand/antagonists & inhibitors ; Structure-Activity Relationship
Keywords
Bone Disease ; NMR ; OPG Analogue Peptides ; Osteoprotegerin
Abstract
Osteoprotegerin (OPG) is a soluble decoy receptor that inhibits osteoclastogenesis and is closely associated with bone resorption processes. We have designed and determined the solution structures of potent OPG analogue peptides, derived from sequences of the cysteine-rich domain of OPG. The inhibitory effects of the peptides on osteoclastogenesis are dose-dependent (10(-6) M-10(-4) M), and the activity of the linear peptide at 10(-4) M is ten-fold higher than that of the cyclic OPG peptide. Both linear and cyclic peptides have a beta-turn-like conformation and the cyclic peptide has a rigid conformation, suggesting that structural flexibility is an important factor for receptor binding. Based on structural and biochemical information about RANKL and the OPG peptides, we suggest that complex formation between the peptide and RANKL is mediated by both hydrophobic and hydrogen bonding interactions. These results provide structural insights that should aid in the design of peptidyl-mimetic inhibitors for treating metabolic bone diseases caused by abnormal osteoclast recruitment
Full Text
http://www.molcells.org/journal/view.html?year=2008&volume=25&number=3&spage=352
DOI
18443424
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Lim, Sung Kil(임승길)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/107019
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