2ewy: Difference between revisions
No edit summary |
No edit summary |
||
| Line 1: | Line 1: | ||
[[Image:2ewy.gif|left|200px]] | [[Image:2ewy.gif|left|200px]] | ||
<!-- | |||
The line below this paragraph, containing "STRUCTURE_2ewy", creates the "Structure Box" on the page. | |||
You may change the PDB parameter (which sets the PDB file loaded into the applet) | |||
or the SCENE parameter (which sets the initial scene displayed when the page is loaded), | |||
or leave the SCENE parameter empty for the default display. | |||
| | --> | ||
| | {{STRUCTURE_2ewy| PDB=2ewy | SCENE= }} | ||
}} | |||
'''Crystal structure of human BACE2 in complex with a hydroxyethylenamine transition-state inhibitor''' | '''Crystal structure of human BACE2 in complex with a hydroxyethylenamine transition-state inhibitor''' | ||
| Line 27: | Line 24: | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Ostermann, N.]] | [[Category: Ostermann, N.]] | ||
[[Category: | [[Category: Aspartic protease]] | ||
[[Category: | [[Category: Bace2]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 03:12:28 2008'' | |||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | |||
Revision as of 03:12, 4 May 2008
Crystal structure of human BACE2 in complex with a hydroxyethylenamine transition-state inhibitor
OverviewOverview
BACE2 is a membrane-bound aspartic protease of the A1 family with a high level of sequence homology to BACE1. While BACE1 is involved in the generation of amyloid plaques in Alzheimer's disease by cleaving Abeta-peptides from the amyloid precursor protein, the physiological function of BACE2 is not well understood. BACE2 appears to be associated with the early onset of dementia in patients with Down's syndrome, and it has been shown to be highly expressed in breast cancers. Further, it may participate in the function of normal and abnormal processes of human muscle biology. Similar to other aspartic proteases, BACE2 is expressed as an inactive zymogen requiring the cleavage of its pro-sequence during the maturation process. We have produced mature BACE2 by expression of pro-BACE2 in Escherichia coli as inclusion bodies, followed by refolding and autocatalytic activation at pH 3.4. Using a C and N-terminally truncated BACE2 variant, we were able to crystallize and determine the crystal structure of mature BACE2 in complex with a hydroxyethylamine transition-state mimetic inhibitor at 3.1 angstroms resolution. The structure of BACE2 follows the general fold of A1 aspartic proteases. However, similar to BACE1, its C-terminal domain is significantly larger than that of the other family members. Furthermore, the structure of BACE2 reveals differences in the S3, S2, S1' and S2' active site substrate pockets as compared to BACE1, and allows, therefore, for a deeper understanding of the structural features that may facilitate the design of selective BACE1 or BACE2 inhibitors.
About this StructureAbout this Structure
2EWY is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
Crystal structure of human BACE2 in complex with a hydroxyethylamine transition-state inhibitor., Ostermann N, Eder J, Eidhoff U, Zink F, Hassiepen U, Worpenberg S, Maibaum J, Simic O, Hommel U, Gerhartz B, J Mol Biol. 2006 Jan 13;355(2):249-61. Epub 2005 Nov 8. PMID:16305800 Page seeded by OCA on Sun May 4 03:12:28 2008