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SUMMARY:Crystal Structure of Human Insulin-Regulated Aminopeptidase
DTSTART;VALUE=DATE-TIME:20141121T012500Z
DTEND;VALUE=DATE-TIME:20141121T014500Z
DTSTAMP;VALUE=DATE-TIME:20260712T173608Z
UID:indico-contribution-670@events01.synchrotron.org.au
DESCRIPTION:Speakers: Stefan Hermans (St Vincent's Institute)\nDementia is
  the single greatest cause of disability in older Australians afflicting a
 lmost one in ten over the age of 65. In the absence of curative therapies\
 , current treatments aimed at enhancing working memory target the choliner
 gic system and demonstrate limited efficacy\, underpinning the need for a 
 new class of cognitive enhancing drug. Insulin-regulated aminopeptidase (I
 RAP) is a membrane-bound zinc-metallopeptidase that cleaves neuroactive pe
 ptides in the brain and its inhibition gives rise to memory enhancing effe
 cts in both normal and memory-impaired rodents . Using a large scale insec
 t cell expression system to produce milligram quantities of protein suitab
 le for crystallography\, and the Micro Crystallography Beamline at the Aus
 tralian Synchrotron\, we have determined the crystal structure of human IR
 AP to 2.96 Å. This structure revealed a semi-closed\, four domain arrange
 ment with a large\, mostly buried cavity adjacent to the active site as we
 ll as a dimer interface located in the C-terminal domain. A comparison of 
 the catalytic domain with related aminopeptidases revealed a strikingly di
 fferent conformation of the GAMEN exopeptidase loop that explains IRAP’s
  unique specificity for cyclic peptides such as oxytocin and vasopressin. 
 This structure will be a powerful tool in the development of new classes o
 f cognitive enhancers for treating memory disorders such as Alzheimer's de
 mentia.\n\nhttps://events01.synchrotron.org.au/event/3/contributions/670/
LOCATION: Oliphant Auditorium
URL:https://events01.synchrotron.org.au/event/3/contributions/670/
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