6LCS

Crystal structure of 73MuL9 Fv-clasp fragment in complex with GA-pyridine analogue

6LCS の概要

• エントリーDOI: 10.2210/pdb6lcs/pdb
• 分子名称: VH-SARAH, VL-SARAH, (2~{S})-6-[4-(hydroxymethyl)-3-oxidanyl-pyridin-1-ium-1-yl]-2-(phenylmethoxycarbonylamino)hexanoic acid, ... (5 entities in total)
• 機能のキーワード: age, antibody fragment, fv-clasp, immune system
• 由来する生物種: Mus musculus; 詳細
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 38666.98

構造登録者

Nakamura, T.,Takagi, J.,Yamagata, Y.,Morioka, H. (登録日: 2019-11-19, 公開日: 2020-11-25, 最終更新日: 2024-11-13)

主引用文献

Kobashigawa, Y.,Ohara, T.,Morita, K.,Toyota, Y.,Nakamura, T.,Kotani, S.,Arimori, T.,Yamauchi, S.,Liu, C.,Kitazaki, M.,Wakeyama-Miyazaki, Y.,Suwa, Y.,Uchida-Kamekura, M.,Fukuda, N.,Sato, T.,Nakajima, M.,Takagi, J.,Yamagata, Y.,Morioka, H.
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.
J.Biochem., 170:379-387, 2021

PubMed Abstract: 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.

PubMed: 34185078
DOI: 10.1093/jb/mvab056

実験手法

X-RAY DIFFRACTION (2.6 Å)