Structure of uncomplexed and linoleate-bound Candida cylindracea cholesterol esterase

Debashis Ghosh*, Zdzislaw Wawrzak, Vladimir Z. Pletnev, Naiyin Li, Rudolf Kaiser, Walter Pangborn, Hans Jörnvall, Mary Erman, William L. Duax

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

104 Scopus citations

Abstract

Background: Candida cylindracea cholesterol esterase (CE) reversibly hydrolyzes cholesteryl linoleate and oleate. CE belongs to the same α/β hydrolase superfamily as triacylglycerol acyl hydrolases and cholinesterases. Other members of the family that have been studied by X-ray crystallography include Torpedo californica acetylcholinesterase, Geotrichum candidum lipase and Candida rugosa lipase. CE is homologous to C. rugosa lipase 1, a triacylglycerol acyl hydrolase, with which it shares 89% sequence identity. The present study explores the details of dimer formation of CE and the basis for its substrate specificity. Results The structures of uncomplexed and linoleate-bound CE determined at 1.9 å and 2.0 å resolution, respectively, reveal a dimeric association of monomers in which two active-site gorges face each other, shielding hydrophobic surfaces from the aqueous environment. The fatty-acid chain is buried in a deep hydrophobic pocket near the active site. The positioning of the cholesteryl moiety of the substrate is equivocal, but could be modeled in the hydrophobic core of the dimer interface. Conclusion The monomer structure is the same in both the complexed and uncomplexed crystal forms. The dimers differ in the relative positions of the two monomers at the dimer interface. Of the 55 residues that are different in CE from those in C. rugosa lipase 1, 23 are located in the active site and at the dimer interface. The altered substrate specificity is a direct consequence of these substitutions.

Original languageEnglish (US)
Pages (from-to)279-288
Number of pages10
JournalStructure
Volume3
Issue number3
DOIs
StatePublished - Mar 1995

Keywords

  • X-ray structure
  • cholesterol esterase
  • cholesteryl linoleate
  • dimer formation
  • hydrolysis and esterification

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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