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2ohr

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Revision as of 09:01, 18 October 2017

X-ray crystal structure of beta secretase complexed with compound 6a

Structural highlights

2ohr is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Related:	2of0, 2ohk, 2ohl, 2ohm, 2ohn, 2ohp, 2ohq, 2ohs, 2oht, 2ohu
Gene:	BACE1, BACE (HUMAN)
Activity:	Memapsin 2, with EC number 3.4.23.46
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[BACE1_HUMAN] Responsible for the proteolytic processing of the amyloid precursor protein (APP). Cleaves at the N-terminus of the A-beta peptide sequence, between residues 671 and 672 of APP, leads 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.^[1] ^[2]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Fragment-based lead discovery has been successfully applied to the aspartyl protease enzyme beta-secretase (BACE-1). Fragment hits that contained an aminopyridine motif binding to the two catalytic aspartic acid residues in the active site of the enzyme were the chemical starting points. Structure-based design approaches have led to identification of low micromolar lead compounds that retain these interactions and additionally occupy adjacent hydrophobic pockets of the active site. These leads form two subseries, for which compounds 4 (IC50 = 25 microM) and 6c (IC50 = 24 microM) are representative. In the latter series, further optimization has led to 8a (IC50 = 690 nM).

Application of fragment screening by X-ray crystallography to the discovery of aminopyridines as inhibitors of beta-secretase.,Congreve M, Aharony D, Albert J, Callaghan O, Campbell J, Carr RA, Chessari G, Cowan S, Edwards PD, Frederickson M, McMenamin R, Murray CW, Patel S, Wallis N J Med Chem. 2007 Mar 22;50(6):1124-32. Epub 2007 Feb 22. PMID:17315857^[3]

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

References

↑ Lin X, Koelsch G, Wu S, Downs D, Dashti A, Tang J. Human aspartic protease memapsin 2 cleaves the beta-secretase site of beta-amyloid precursor protein. Proc Natl Acad Sci U S A. 2000 Feb 15;97(4):1456-60. PMID:10677483
↑ Okada H, Zhang W, Peterhoff C, Hwang JC, Nixon RA, Ryu SH, Kim TW. Proteomic identification of sorting nexin 6 as a negative regulator of BACE1-mediated APP processing. FASEB J. 2010 Aug;24(8):2783-94. doi: 10.1096/fj.09-146357. Epub 2010 Mar 30. PMID:20354142 doi:10.1096/fj.09-146357
↑ Congreve M, Aharony D, Albert J, Callaghan O, Campbell J, Carr RA, Chessari G, Cowan S, Edwards PD, Frederickson M, McMenamin R, Murray CW, Patel S, Wallis N. Application of fragment screening by X-ray crystallography to the discovery of aminopyridines as inhibitors of beta-secretase. J Med Chem. 2007 Mar 22;50(6):1124-32. Epub 2007 Feb 22. PMID:17315857 doi:10.1021/jm061197u

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2ohr"

@@ Line 1: / Line 1: @@
 ==X-ray crystal structure of beta secretase complexed with compound 6a==
 <StructureSection load='2ohr' size='340' side='right' caption='[[2ohr]], [[Resolution|resolution]] 2.25&Aring;' scene=''>
@@ Line 7: / Line 8: @@
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">BACE1, BACE ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
 <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Memapsin_2 Memapsin 2], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.46 3.4.23.46] </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=2ohr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ohr OCA], [http://pdbe.org/2ohr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ohr RCSB], [http://www.ebi.ac.uk/pdbsum/2ohr 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=2ohr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2ohr OCA], [http://pdbe.org/2ohr PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2ohr RCSB], [http://www.ebi.ac.uk/pdbsum/2ohr PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2ohr ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 30: / Line 31: @@
 </div>
 <div class="pdbe-citations 2ohr" style="background-color:#fffaf0;"></div>
-==See Also==
-*[[Beta secretase|Beta secretase]]
 == References ==
 <references/>

2ohr

From Proteopedia

Revision as of 09:01, 18 October 2017

X-ray crystal structure of beta secretase complexed with compound 6a

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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