Characterization of alpha-nitromethyl ketone as a new zinc-binding group based on structural analysis of its complex with carboxypeptidase A.
Zinc-binding groups (ZBGs) are exhaustively applied in the development of the new inhibitors against a wide variety of physiologically and pathologically important zinc proteases. Here the alpha-nitro ketone was presented as a new ZBG, which is a transition-state analog featured by the unique bifurcated hydrogen bonds at the active site of carboxypeptidase A based on the structural analysis. Introduction of a nitro group at the alpha-position of the ketone could provide more non-covalent interactions without loss of the abilities to form a tetrahedral transition-state analog.
Wang
Shou-Feng
SF
Key Laboratory of Biological Resources and Functional Molecules of the Changbai Mountains, Ministry of Education, Yanbian University, Yanji, Jilin, China.
Tian
Guan Rong
GR
Zhang
Wen-Zheng
WZ
Jin
Jing-Yi
JY
D001665:Binding Sites; D043422:Carboxypeptidases A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D008968:Molecular Conformation; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011485:Protein Binding; D015032:Zinc / Q000737:chemistry*
D007659:Ketones; D011480:Protease Inhibitors; D043422:Carboxypeptidases A; D015032:Zinc