Molecular recognition of a single-chain Fv antibody specific for GA-pyridine, an advanced glycation end-product (AGE), elucidated using biophysical techniques and synthetic antigen analogues

Autor:	Yoshiaki Suwa, Natsuki Fukuda, Takao Arimori, Yuya Toyota, Shunsuke Kotani, Junichi Takagi, Masaya Kitazaki, Soichiro Yamauchi, Yoshihiro Kobashigawa, Hiroshi Morioka, Makiyo Uchida-Kamekura, Yukari Wakeyama-Miyazaki, Kosuke Morita, Yuriko Yamagata, Teruya Nakamura, Toshiya Ohara, Takashi Sato, Chenjiang Liu, Makoto Nakajima
Rok vydání:	2021
Předmět:	Glycation End Products Advanced Glycolaldehyde Crystallography Pyridines Synthetic antigen Biophysics Substituent Chemical biology Hydrogen Bonding Acetaldehyde General Medicine Biochemistry chemistry.chemical_compound Molecular recognition chemistry Structural biology Glycation Humans Thermodynamics Advanced glycation end-product Amino Acid Sequence Antigens Molecular Biology Single-Chain Antibodies
Zdroj:	The Journal of Biochemistry. 170:379-387
ISSN:	1756-2651 0021-924X
Popis:	Advanced glycation end-products (AGEs) are a heterogeneous group of compounds formed by non-enzymatic reaction between reducing-sugar and Arg/Lys in proteins and are involved in various diabetic complications. GA-pyridine is derived from glycolaldehyde and is one of the most cytotoxic AGEs. Here, we established a single-chain Fv (scFv) antibody against GA-pyridine, 73MuL9-scFv, and examined the details of its specificity and antigen recognition by using various techniques involving biophysics, chemical biology and structural biology. We also synthesized several compounds that differ slightly in regard to the position and number of GA-pyridine substituent groups, and revealed that GA-pyridine was specifically bound to 73MuL9-scFv. Thermodynamic analysis revealed that the association of GA-pyridine to 73MuL9-scFv was an exothermic and enthalpy driven reaction, and thus that the antigen recognition involved multiple specific interactions. Crystallographic analysis of the Fv fragment of 73MuL9-scFv revealed that several CH-π and hydrogen bond interactions took place between the Fv-fragment and GA-pyridine, which was consistent with the results of thermodynamic analysis. Further studies using 73MuL9-scFv as a tool to clarify the relevance of GA-pyridine to diabetic complications are warranted.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7bf5f143b2dea1431710627728098d31 https://doi.org/10.1093/jb/mvab056 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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