2zht

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'''Crystal structure of BACE1 at pH 4.5'''
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===Crystal structure of BACE1 at pH 4.5===
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==Overview==
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BACE1 (beta-secretase) is a transmembrane aspartic protease that cleaves the beta-amyloid precursor protein (APP) and generates the amyloid beta peptide (Abeta). BACE1 cycles between the cell surface and the endosomal system many times, and becomes activated interconvertibly during its cellular trafficking, leading to the production of Abeta. Here we report the crystal structure of the catalytically active form of BACE1. The active form has novel structural features involving the conformation of the flap and subsites that promote substrate binding. The functionally essential residues and water molecules are well defined, playing a key role in the iterative activation of BACE1. Furthermore, we describe the crystal structure of the dehydrated form of BACE1, showing that BACE1 activity is dependent on the dynamics of a catalytically required Asp-bound water molecule, which directly affects its catalytic properties. These findings provide insight into a novel regulation of BACE1 activity and elucidate how BACE1 modulates its activity during cellular trafficking.
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==About this Structure==
==About this Structure==
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[[Category: Transmembrane]]
[[Category: Transmembrane]]
[[Category: Zymogen]]
[[Category: Zymogen]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Apr 24 09:46:45 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 19:05:04 2008''

Revision as of 16:05, 27 July 2008

Image:2zht.png


PDB ID 2zht

Drag the structure with the mouse to rotate
2zht, resolution 2.35Å ()
Gene: BACE1 (Homo sapiens)
Activity: Memapsin 2, with EC number 3.4.23.46
Related: 2zhr, 2zhs, 2zhu, 2zhv
Resources: FirstGlance, OCA, PDBsum, RCSB
Coordinates: save as pdb, mmCIF, xml



Crystal structure of BACE1 at pH 4.5

Template:ABSTRACT PUBMED 18378702

About this Structure

2ZHT is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Crystal structure of an active form of BACE1: an enzyme responsible for amyloid {beta} protein production., Shimizu H, Tosaki A, Kaneko K, Hisano T, Sakurai T, Nukina N, Mol Cell Biol. 2008 Mar 31;. PMID:18378702

Page seeded by OCA on Sun Jul 27 19:05:04 2008

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