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3zl7

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Revision as of 14:07, 4 August 2016

BACE2 FYNOMER COMPLEX

Structural highlights

3zl7 is a 2 chain structure with sequence from Human and Synthetic construct sequences. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Related:	3zkg, 3zki, 3zkm, 3zkn, 3zkq, 3zks
Activity:	Memapsin 1, with EC number 3.4.23.45
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[BACE2_HUMAN] Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves APP, between residues 690 and 691, leading to the generation and extracellular release of beta-cleaved soluble APP, and a corresponding cell-associated C-terminal fragment which is later released by gamma-secretase. It has also been shown that it can cleave APP between residues 671 and 672.^[1] ^[2] ^[3] ^[4] ^[5]

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^[6]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Yan R, Bienkowski MJ, Shuck ME, Miao H, Tory MC, Pauley AM, Brashier JR, Stratman NC, Mathews WR, Buhl AE, Carter DB, Tomasselli AG, Parodi LA, Heinrikson RL, Gurney ME. Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity. Nature. 1999 Dec 2;402(6761):533-7. PMID:10591213 doi:10.1038/990107
↑ Hussain I, Powell DJ, Howlett DR, Chapman GA, Gilmour L, Murdock PR, Tew DG, Meek TD, Chapman C, Schneider K, Ratcliffe SJ, Tattersall D, Testa TT, Southan C, Ryan DM, Simmons DL, Walsh FS, Dingwall C, Christie G. ASP1 (BACE2) cleaves the amyloid precursor protein at the beta-secretase site. Mol Cell Neurosci. 2000 Nov;16(5):609-19. PMID:11083922 doi:10.1006/mcne.2000.0884
↑ Sun X, Wang Y, Qing H, Christensen MA, Liu Y, Zhou W, Tong Y, Xiao C, Huang Y, Zhang S, Liu X, Song W. Distinct transcriptional regulation and function of the human BACE2 and BACE1 genes. FASEB J. 2005 May;19(7):739-49. PMID:15857888 doi:10.1096/fj.04-3426com
↑ Yan R, Munzner JB, Shuck ME, Bienkowski MJ. BACE2 functions as an alternative alpha-secretase in cells. J Biol Chem. 2001 Sep 7;276(36):34019-27. Epub 2001 Jun 22. PMID:11423558 doi:10.1074/jbc.M105583200
↑ Sun X, He G, Song W. BACE2, as a novel APP theta-secretase, is not responsible for the pathogenesis of Alzheimer's disease in Down syndrome. FASEB J. 2006 Jul;20(9):1369-76. PMID:16816112 doi:10.1096/fj.05-5632com
↑ 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. Mapping the conformational space accessible to BACE2 using surface mutants and cocrystals with Fab fragments, Fynomers and Xaperones. Acta Crystallogr D Biol Crystallogr. 2013 Jun;69(Pt 6):1124-37. doi:, 10.1107/S0907444913006574. Epub 2013 May 15. PMID:23695257 doi:10.1107/S0907444913006574

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3zl7"

@@ Line 1: / Line 1: @@
 ==BACE2 FYNOMER COMPLEX==
 <StructureSection load='3zl7' size='340' side='right' caption='[[3zl7]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[3zl7]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [http://en.wikipedia.org/wiki/Synthetic_construct Synthetic construct]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZL7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZL7 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[3zl7]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human] and [http://en.wikipedia.org/wiki/Synthetic_construct_sequences Synthetic construct sequences]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3ZL7 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3ZL7 FirstGlance]. <br>
 </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3zkg|3zkg]], [[3zki|3zki]], [[3zkm|3zkm]], [[3zkn|3zkn]], [[3zkq|3zkq]], [[3zks|3zks]]</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Memapsin_1 Memapsin 1], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.45 3.4.23.45] </span></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3zl7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zl7 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3zl7 RCSB], [http://www.ebi.ac.uk/pdbsum/3zl7 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3zl7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3zl7 OCA], [http://pdbe.org/3zl7 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3zl7 RCSB], [http://www.ebi.ac.uk/pdbsum/3zl7 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3zl7 ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 3zl7" style="background-color:#fffaf0;"></div>
 ==See Also==
@@ Line 24: / Line 26: @@
 __TOC__
 </StructureSection>
-[[Category: Homo sapiens]]
+[[Category: Human]]
 [[Category: Memapsin 1]]
-[[Category: Synthetic construct]]
+[[Category: Synthetic construct sequences]]
 [[Category: Banner, D W]]
 [[Category: Benz, J]]

3zl7

From Proteopedia

Revision as of 14:07, 4 August 2016

BACE2 FYNOMER COMPLEX

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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