Structural basis for the β-lactamase activity of EstU1, a family VIII carboxylesterase

Sun Shin Cha, Young Jun An, Chang Sook Jeong, Min Kyu Kim, Jeong Ho Jeon, Chang Muk Lee, Hyun Sook Lee, Sung Gyun Kang, Jung Hyun Lee

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33 Scopus citations


EstU1 is a unique family VIII carboxylesterase that displays hydrolytic activity toward the amide bond of clinically used β-lactam antibiotics as well as the ester bond of p-nitrophenyl esters. EstU1 assumes a β-lactamase-like modular architecture and contains the residues Ser100, Lys103, and Tyr218, which correspond to the three catalytic residues (Ser64, Lys67, and Tyr150, respectively) of class C β-lactamases. The structure of the EstU1/cephalothin complex demonstrates that the active site of EstU1 is not ideally tailored to perform an efficient deacylation reaction during the hydrolysis of β-lactam antibiotics. This result explains the weak β-lactamase activity of EstU1 compared with class C β-lactamases. Finally, structural and sequential comparison of EstU1 with other family VIII carboxylesterases elucidates an operative molecular strategy used by family VIII carboxylesterases to extend their substrate spectrum.

Original languageEnglish
Pages (from-to)2045-2051
Number of pages7
JournalProteins: Structure, Function and Bioinformatics
Issue number11
StatePublished - Nov 2013


  • Crystal structure of EstU1
  • Crystal structure of the EstU1/cephalothin complex
  • EstU1
  • Family VIII carboxylesterases
  • β-lactamase activity


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