TY - JOUR
T1 - S100B as an Antagonist to Interfere with the Interface Area Flanked by S100A11 and RAGE v Domain
AU - Dowarha, Deepu
AU - Chou, Ruey Hwang
AU - Yu, Chin
N1 - Funding Information:
*E-mail: [email protected]. Fax: 886-35-711082. ORCID Chin Yu: 0000-0002-1564-8040 Funding This research was sponsored by the Ministry of Science and Technology (MOST) of Taiwan (Grant number MOST 104-2113-M-007-019-MY3) and in part by China Medical University (Grant number CMU104-S-02, Taiwan). Notes The authors declare no competing financial interest.
Publisher Copyright:
Copyright © 2018 American Chemical Society.
PY - 2018/8/31
Y1 - 2018/8/31
N2 - The Ca2+-sensing protein S100A11 of the S100 family is an important mediator of numerous biological functions and pathological conditions including cancer. The receptor for advanced glycation end products (RAGE) has been well accepted as the major receptor for several S100 family members. Here, we take the S100B protein as an antagonist to interfere with the interaction flanked by S100A11 and the RAGE V domain. We employed NMR spectroscopy to describe the interactions between the S100A11 and S100B proteins. 1H-15N heteronuclear single-quantum correlation-NMR titrations showed the potential binding dynamics of S100A11 and S100B interactions. In the HADDOCK program, we constructed the S100A11-S100B heterodimer complex that was then superimposed with the S100A11-S100B complex structure in the same orientation as the S100A11-RAGE V domain complex. This overlay analysis showed that S100B could interfere in the binding section of S100A11 and the RAGE V domain. Additionally, water-soluble tetrazolium-1 assay provided a functional read-out of the effects of these proteins in an in vitro cancer model. Our study establishes that the development of an S100B antagonist could perform a vital part in the treatment of S100- and RAGE-dependent human diseases.
AB - The Ca2+-sensing protein S100A11 of the S100 family is an important mediator of numerous biological functions and pathological conditions including cancer. The receptor for advanced glycation end products (RAGE) has been well accepted as the major receptor for several S100 family members. Here, we take the S100B protein as an antagonist to interfere with the interaction flanked by S100A11 and the RAGE V domain. We employed NMR spectroscopy to describe the interactions between the S100A11 and S100B proteins. 1H-15N heteronuclear single-quantum correlation-NMR titrations showed the potential binding dynamics of S100A11 and S100B interactions. In the HADDOCK program, we constructed the S100A11-S100B heterodimer complex that was then superimposed with the S100A11-S100B complex structure in the same orientation as the S100A11-RAGE V domain complex. This overlay analysis showed that S100B could interfere in the binding section of S100A11 and the RAGE V domain. Additionally, water-soluble tetrazolium-1 assay provided a functional read-out of the effects of these proteins in an in vitro cancer model. Our study establishes that the development of an S100B antagonist could perform a vital part in the treatment of S100- and RAGE-dependent human diseases.
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U2 - 10.1021/acsomega.8b00922
DO - 10.1021/acsomega.8b00922
M3 - Article
AN - SCOPUS:85052378516
SN - 2470-1343
VL - 3
SP - 9689
EP - 9698
JO - ACS Omega
JF - ACS Omega
IS - 8
ER -