3cib

From Proteopedia

(Difference between revisions)

Current revision

Structure of BACE Bound to SCH727596

Structural highlights

3cib is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.72Å
Ligands:	,
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

Guided by structure-based design, we synthesized two novel series of potent inhibitors of BACE1 and generated extensive SAR around both the prime and non-prime side binding pockets. The key feature of both series is a cyclic amine motif specifically crafted to achieve interactions with both the flap and with the S2' pocket.

Rational design of novel, potent piperazinone and imidazolidinone BACE1 inhibitors.,Cumming JN, Le TX, Babu S, Carroll C, Chen X, Favreau L, Gaspari P, Guo T, Hobbs DW, Huang Y, Iserloh U, Kennedy ME, Kuvelkar R, Li G, Lowrie J, McHugh NA, Ozgur L, Pan J, Parker EM, Saionz K, Stamford AW, Strickland C, Tadesse D, Voigt J, Wang L, Wu Y, Zhang L, Zhang Q Bioorg Med Chem Lett. 2008 Jun 1;18(11):3236-41. Epub 2008 Apr 25. PMID:18468890^[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
↑ Cumming JN, Le TX, Babu S, Carroll C, Chen X, Favreau L, Gaspari P, Guo T, Hobbs DW, Huang Y, Iserloh U, Kennedy ME, Kuvelkar R, Li G, Lowrie J, McHugh NA, Ozgur L, Pan J, Parker EM, Saionz K, Stamford AW, Strickland C, Tadesse D, Voigt J, Wang L, Wu Y, Zhang L, Zhang Q. Rational design of novel, potent piperazinone and imidazolidinone BACE1 inhibitors. Bioorg Med Chem Lett. 2008 Jun 1;18(11):3236-41. Epub 2008 Apr 25. PMID:18468890 doi:http://dx.doi.org/10.1016/j.bmcl.2008.04.050

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

Categories: Homo sapiens | Large Structures | Cumming J | Strickland C

@@ Line 1: / Line 1: @@
-[[Image:3cib.jpg|left|200px]]
-<!--
+==Structure of BACE Bound to SCH727596==
-The line below this paragraph, containing "STRUCTURE_3cib", creates the "Structure Box" on the page.
+<StructureSection load='3cib' size='340' side='right'caption='[[3cib]], [[Resolution|resolution]] 1.72&Aring;' scene=''>
-You may change the PDB parameter (which sets the PDB file loaded into the applet)
+== Structural highlights ==
-or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
+<table><tr><td colspan='2'>[[3cib]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CIB OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CIB FirstGlance]. <br>
-or leave the SCENE parameter empty for the default display.
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.72&#8491;</td></tr>
--->
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=314:N-[(1S,2R)-2-[(2R,4S)-4-BENZYLPIPERIDIN-2-YL]-1-(3,5-DIFLUOROBENZYL)-2-HYDROXYETHYL]-5-METHYL-N,N-DIPROPYLBENZENE-1,3-DICARBOXAMIDE'>314</scene>, <scene name='pdbligand=TAR:D(-)-TARTARIC+ACID'>TAR</scene></td></tr>
-{{STRUCTURE_3cib|  PDB=3cib  |  SCENE=  }}
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3cib FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3cib OCA], [https://pdbe.org/3cib PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3cib RCSB], [https://www.ebi.ac.uk/pdbsum/3cib PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3cib ProSAT]</span></td></tr>
+</table>
+== Function ==
+[https://www.uniprot.org/uniprot/BACE1_HUMAN 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.<ref>PMID:10677483</ref> <ref>PMID:20354142</ref>
+== Evolutionary Conservation ==
+[[Image:Consurf_key_small.gif|200px|right]]
+Check<jmol>
+  <jmolCheckbox>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ci/3cib_consurf.spt"</scriptWhenChecked>
+    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
+    <text>to colour the structure by Evolutionary Conservation</text>
+  </jmolCheckbox>
+</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=3cib ConSurf].
+<div style="clear:both"></div>
+<div style="background-color:#fffaf0;">
+== Publication Abstract from PubMed ==
+Guided by structure-based design, we synthesized two novel series of potent inhibitors of BACE1 and generated extensive SAR around both the prime and non-prime side binding pockets. The key feature of both series is a cyclic amine motif specifically crafted to achieve interactions with both the flap and with the S2' pocket.
-'''Structure of BACE Bound to SCH727596'''
+Rational design of novel, potent piperazinone and imidazolidinone BACE1 inhibitors.,Cumming JN, Le TX, Babu S, Carroll C, Chen X, Favreau L, Gaspari P, Guo T, Hobbs DW, Huang Y, Iserloh U, Kennedy ME, Kuvelkar R, Li G, Lowrie J, McHugh NA, Ozgur L, Pan J, Parker EM, Saionz K, Stamford AW, Strickland C, Tadesse D, Voigt J, Wang L, Wu Y, Zhang L, Zhang Q Bioorg Med Chem Lett. 2008 Jun 1;18(11):3236-41. Epub 2008 Apr 25. PMID:18468890<ref>PMID:18468890</ref>
-==Overview==
-Guided by structure-based design, we synthesized two novel series of potent inhibitors of BACE1 and generated extensive SAR around both the prime and non-prime side binding pockets. The key feature of both series is a cyclic amine motif specifically crafted to achieve interactions with both the flap and with the S2' pocket.
-==About this Structure==
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
-CIB is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3CIB OCA].
+</div>
+<div class="pdbe-citations 3cib" style="background-color:#fffaf0;"></div>
-==Reference==
+==See Also==
-Rational design of novel, potent piperazinone and imidazolidinone BACE1 inhibitors., Cumming JN, Le TX, Babu S, Carroll C, Chen X, Favreau L, Gaspari P, Guo T, Hobbs DW, Huang Y, Iserloh U, Kennedy ME, Kuvelkar R, Li G, Lowrie J, McHugh NA, Ozgur L, Pan J, Parker EM, Saionz K, Stamford AW, Strickland C, Tadesse D, Voigt J, Wang L, Wu Y, Zhang L, Zhang Q, Bioorg Med Chem Lett. 2008 Jun 1;18(11):3236-41. Epub 2008 Apr 25. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18468890 18468890]
+*[[Beta secretase 3D structures|Beta secretase 3D structures]]
+== References ==
+<references/>
+__TOC__
+</StructureSection>
 [[Category: Homo sapiens]]
-[[Category: Memapsin 2]]
+[[Category: Large Structures]]
-[[Category: Single protein]]
+[[Category: Cumming J]]
-[[Category: Cumming, J.]]
+[[Category: Strickland C]]
-[[Category: Strickland, C.]]
-[[Category: Aspartyl protease]]
-[[Category: Bace1]]
-[[Category: Hydrolase]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jun 11 10:49:26 2008''

3cib

From Proteopedia

Current revision

Structure of BACE Bound to SCH727596

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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