The crystal structure of an HSL-homolog EstE5 complex with PMSF reveals a unique configuration that inhibits the nucleophile Ser144 in catalytic triads

Biochem Biophys Res Commun. 2009 Nov 13;389(2):247-50. doi: 10.1016/j.bbrc.2009.08.123. Epub 2009 Aug 26.


The esterase/lipase family (EC represents a diverse group of hydrolases that catalyze the cleavage of ester bonds and are widely distributed in animals, plants and microorganisms. Among these enzymes, hormone-sensitive lipases, play a critical role in the regulation of rodent fat cell lipolysis and are regarded as adipose tissue-specific enzymes. Recently, we reported the structural and biological characterization of EstE5 from the metagenome library [K.H. Nam, M.Y. Kim, S.J. Kim, A. Priyadarshi, W.H. Lee, K.Y. Hwang, Structural and functional analysis of a novel EstE5 belonging to the subfamily of hormone-sensitive lipase, Biochem. Biophys. Res. Commun. 379 (2009) 553-556]. The structure of this protein revealed that it belongs to the HSL-family. Here, we report the inhibition of the activity of the HSL-homolog EstE5 protein as determined by the use of esterase/lipase inhibitors. Our results revealed that the EstE5 protein is significantly inhibited by PMSF. In addition, this is the first study to identify the crystal structures of EstE5-PMSF at 2.4 and 2.5A among the HSL-homolog structures. This structural configuration is similar to that adopted when serine proteases are inhibited by PMSF. The results presented here provide valuable information regarding the properties of the HSL-family.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Catalysis
  • Catalytic Domain
  • Crystallography, X-Ray
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / pharmacology
  • Protein Conformation
  • Serine / chemistry*
  • Sterol Esterase / antagonists & inhibitors*
  • Sterol Esterase / chemistry*
  • Tosyl Compounds / chemistry*
  • Tosyl Compounds / pharmacology


  • Protease Inhibitors
  • Tosyl Compounds
  • Serine
  • 4-toluenesulfonyl fluoride
  • Sterol Esterase