4bfb | pdb_00004bfb

BACE2 XAPERONE COMPLEX

spinqualitylabelsall models 4bfb, resolution 2.21Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4bfb is a 4 chain structure with sequence from Homo sapiens and Lama glama. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: B3P Related: 4bek, 4bel, 3zkg, 3zki, 3zkm, 3zkn, 3zkq, 3zks, 3zkx, 3zl7, 3zov Activity: Memapsin 1, with EC number 3.4.23.45 Resources: FirstGlance, OCA, RCSB, PDBsum Publication Abstract from PubMed The aspartic protease BACE2 is responsible for the shedding of the transmembrane protein Tmem27 from the surface of pancreatic beta-cells, which leads to inactivation of the beta-cell proliferating activity of Tmem27. This role of BACE2 in the control of beta-cell maintenance suggests BACE2 as a drug target for diabetes. Inhibition of BACE2 has recently been shown to lead to improved control of glucose homeostasis and to increased insulin levels in insulin-resistant mice. BACE2 has 52% sequence identity to the well studied Alzheimer's disease target enzyme beta-secretase (BACE1). High-resolution BACE2 structures would contribute significantly to the investigation of this enzyme as either a drug target or anti-target. Surface mutagenesis, BACE2-binding antibody Fab fragments, single-domain camelid antibody VHH fragments (Xaperones) and Fyn-kinase-derived SH3 domains (Fynomers) were used as crystallization helpers to obtain the first high-resolution structures of BACE2. Eight crystal structures in six different packing environments define an ensemble of low-energy conformations available to the enzyme. Here, the different strategies used for raising and selecting BACE2 binders for cocrystallization are described and the crystallization success, crystal quality and the time and resources needed to obtain suitable crystals are compared. Mapping the conformational space accessible to BACE2 using surface mutants and cocrystals with Fab fragments, Fynomers and Xaperones.,Banner DW, Gsell B, Benz J, Bertschinger J, Burger D, Brack S, Cuppuleri S, Debulpaep M, Gast A, Grabulovski D, Hennig M, Hilpert H, Huber W, Kuglstatter A, Kusznir E, Laeremans T, Matile H, Miscenic C, Rufer AC, Schlatter D, Steyaert J, Stihle M, Thoma R, Weber M, Ruf A Acta Crystallogr D Biol Crystallogr. 2013 Jun;69(Pt 6):1124-37. doi:, 10.1107/S0907444913006574. Epub 2013 May 15. PMID:23695257 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Beta secretase

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