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From the same journal

From the same journal

A MODEL FOR INTERFACIAL ACTIVATION IN LIPASES FROM THE STRUCTURE OF A FUNGAL LIPASE-INHIBITOR COMPLEX

Research output: Contribution to journalArticle

Author(s)

  • A M BRZOZOWSKI
  • U DEREWENDA
  • Z S DEREWENDA
  • G G DODSON
  • D M LAWSON
  • J P TURKENBURG
  • F BJORKLING
  • B HUGEJENSEN
  • S A PATKAR
  • L THIM

Department/unit(s)

Publication details

JournalNature
DatePublished - 6 Jun 1991
Issue number6326
Volume351
Number of pages4
Pages (from-to)491-494
Original languageEnglish

Abstract

LIPASES are hydrolytic enzymes which break down triacylglycerides into free fatty acids and glycerols. They have been classified as serine hydrolases owing to their inhibition by diethyl p-nitrophenyl phosphate 1. Lipase activity is greatly increased at the lipid-water interface 2,3, a phenomenon known as interfacial activation. X-ray analysis has revealed the atomic structures of two triacylglycerol lipases, unrelated in sequence: the human pancreatic lipase (hPL) 4, and an enzyme isolated from the fungus Rhizomucor (formerly Mucor) miehei 5 (RmL). In both enzymes the active centres contain structurally analogous Asp-His-Ser triads (characteristic of serine proteinases), which are buried completely beneath a short helical segment, or 'lid'. Here we present the crystal structure (at 3 angstrom resolution) of a complex of R. miehei lipase with n-hexylphosphonate ethyl ester in which the enzyme's active site is exposed by the movement of the helical lid. This movement also increases the nonpolarity of the surface surrounding the catalytic site. We propose that the structure of the enzyme in this complex is equivalent to the activated state generated by the oil-water interface.

    Research areas

  • MIEHEI TRIGLYCERIDE LIPASE, TRANSITION-STATE ANALOG, MACROMOLECULAR STRUCTURES, VENOM PHOSPHOLIPASE-A2, PANCREATIC LIPASE, CRYSTAL-STRUCTURE, REFINEMENT, CRYSTALLOGRAPHY

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