4p8q

Crystal Structure of Human Insulin Regulated Aminopeptidase with Alanine in Active Site

spinqualitylabelsall models 4p8q, resolution 3.02Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4p8q is a 2 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: NAG, UNL, ZN Activity: Cystinyl aminopeptidase, with EC number 3.4.11.3 Resources: FirstGlance, OCA, RCSB, PDBsum Function [LCAP_HUMAN] Release of an N-terminal amino acid, cleaves before cysteine, leucine as well as other amino acids. Degrades peptide hormones such as oxytocin, vasopressin and angiotensin III, and plays a role in maintaining homeostasis during pregnancy. May be involved in the inactivation of neuronal peptides in the brain. Cleaves Met-enkephalin and dynorphin. Binds angiotensin IV and may be the angiotensin IV receptor in the brain. Publication Abstract from PubMed Insulin-regulated aminopeptidase (IRAP, or oxytocinase) is a membrane-bound zinc- metallopeptidase that cleaves neuroactive peptides in the brain and produces memory enhancing effects when inhibited. We have determined the crystal structure of human IRAP revealing a closed, four domain arrangement with a large, mostly buried cavity abutting the active site. The structure reveals that the GAMEN exopeptidase loop adopts a very different conformation from other aminopeptidases, thus explaining IRAP's unique specificity for cyclic peptides such as oxytocin and vasopressin. Computational docking of a series of IRAP-specific cognitive enhancers into the crystal structure provides a molecular basis for their structure-activity relationships and demonstrates that the structure will be a powerful tool in the development of new classes of cognitive enhancers for treating a variety of memory disorders such as Alzheimer's disease. This article is protected by copyright. All rights reserved. Crystal structure of human insulin-regulated aminopeptidase with specificity for cyclic peptides.,Hermans SJ, Ascher DB, Hancock NC, Holien JK, Michell BJ, Chai SY, Morton CJ, Parker MW Protein Sci. 2014 Nov 18. doi: 10.1002/pro.2604. PMID:25408552 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Aminopeptidase

Proteopedia Page Contributors and Editors (what is this?)

OCA