Alteration of substrate selectivity through mutation of two arginine residues in the binding site of amadoriase II from Aspergillus sp

Biochemistry
Xinle WuVincent M Monnier

Abstract

Amadoriases I and II are deglycation isoenzymes from Aspergillus sp. of potential relevance for treatment of diabetic complications resulting from excessive protein glycation. Amadoriase II has a preference for anionic substrate with a K(m) of 0.23 and 2.53 mM for fructosylglycine and fructosylpropylamine, respectively. In contrast, the corresponding K(m) values for amadoriase I are 9.75 and 0.023 mM, respectively. Chemical modification of amadoriase II with p-hydroxyphenylglyoxal, a specific arginine-modifying reagent, resulted in an inhibition of enzyme activity toward fructosylglycine, while having less effect on the enzymatic activity toward fructosylpropylamine. Peptide mapping and subsequent mass spectrometry analysis suggest that Arg(112) is one of the sites of p-hydroxyphenylglyoxal modification. Sequence alignment between amadoriase I and amadoriase II revealed that two glutamic acids in amadoriase I align to Arg(112) and Arg(114) in amadoriase II. Site-directed mutation of amadoriase II (R112E, R114E) resulted in reversal of the enzymatic activities toward fructosylglycine and fructosylpropylamine. Our results suggested that Arg(112) and Arg(114) are responsible for the high affinity of amadoriase II toward anionic su...Continue Reading

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Citations

Dec 13, 2006·Applied Microbiology and Biotechnology·Maki FujiwaraMotoo Arai
Nov 6, 2009·Applied Microbiology and Biotechnology·Jing ZhengZhanglin Lin
Mar 30, 2010·Applied Microbiology and Biotechnology·Zhanglin Lin, Jing Zheng
Jan 29, 2013·Applied Microbiology and Biotechnology·Yu QianZhanglin Lin
Aug 1, 2008·The Journal of Biological Chemistry·François CollardVivien C Yee
Jun 1, 2013·Acta Crystallographica. Section F, Structural Biology and Crystallization Communications·Keke XingWeimin Gong
Jul 23, 2005·Annals of the New York Academy of Sciences·Carmela MennellaVincenzo Fogliano
Nov 19, 2008·Mass Spectrometry Reviews·Vanessa Leah Mendoza, Richard W Vachet
May 2, 2008·Annals of the New York Academy of Sciences·Vincent M MonnierJianye Zhang
Jan 5, 2005·Archives of Biochemistry and Biophysics·Antonia G MillerJuliet A Gerrard
Oct 22, 2003·Archives of Biochemistry and Biophysics·Xinle Wu, Vincent M Monnier
Apr 8, 2015·Acta Crystallographica. Section F, Structural Biology Communications·Weiqiong GanWeimin Gong
Feb 11, 2010·Journal of Diabetes Science and Technology·Stefano FerriKoji Sode

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