6lcs
Crystal structure of 73MuL9 Fv-clasp fragment in complex with GA-pyridine analogueCrystal structure of 73MuL9 Fv-clasp fragment in complex with GA-pyridine analogue
Structural highlights
Publication Abstract from PubMedAdvanced 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-pi 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. 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.,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 J Biochem. 2021 Oct 12;170(3):379-387. doi: 10.1093/jb/mvab056. PMID:34185078[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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