3ckr: Difference between revisions

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{{Seed}}
[[Image:3ckr.png|left|200px]]


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==Crystal structure of BACE-1 in complex with inhibitor==
The line below this paragraph, containing "STRUCTURE_3ckr", creates the "Structure Box" on the page.
<StructureSection load='3ckr' size='340' side='right'caption='[[3ckr]], [[Resolution|resolution]] 2.70&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'>[[3ckr]] is a 3 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=3CKR OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3CKR FirstGlance]. <br>
or leave the SCENE parameter empty for the default display.
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=009:(4S)-1,4-DIBENZYL-N-[(1S,2R)-1-BENZYL-3-{[3-(DIMETHYLAMINO)BENZYL]AMINO}-2-HYDROXYPROPYL]-2-OXOIMIDAZOLIDINE-4-CARBOXAMIDE'>009</scene></td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3ckp|3ckp]]</div></td></tr>
{{STRUCTURE_3ckr|  PDB=3ckr  |  SCENE= }}
<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/Memapsin_2 Memapsin 2], with EC number [https://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'>[https://proteopedia.org/fgij/fg.htm?mol=3ckr FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ckr OCA], [https://pdbe.org/3ckr PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ckr RCSB], [https://www.ebi.ac.uk/pdbsum/3ckr PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ckr 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/ck/3ckr_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.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=3ckr ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
We describe synthesis and evaluation of a series of cyclic urea derivatives with hydroxylethylamine isostere. Modification of P3, P1, and P2' and combination of SAR display a &gt;100-fold increase in potency with good cellular activity (IC(50)=0.15microM) relative to the previously reported compound 3.


===Crystal structure of BACE-1 in complex with inhibitor===
Synthesis, SAR, and X-ray structure of human BACE-1 inhibitors with cyclic urea derivatives.,Park H, Min K, Kwak HS, Koo KD, Lim D, Seo SW, Choi JU, Platt B, Choi DY Bioorg Med Chem Lett. 2008 May 1;18(9):2900-4. Epub 2008 Apr 8. PMID:18434152<ref>PMID:18434152</ref>


From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 3ckr" style="background-color:#fffaf0;"></div>


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==See Also==
The line below this paragraph, {{ABSTRACT_PUBMED_18434152}}, adds the Publication Abstract to the page
*[[Beta secretase 3D structures|Beta secretase 3D structures]]
(as it appears on PubMed at http://www.pubmed.gov), where 18434152 is the PubMed ID number.
== References ==
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<references/>
{{ABSTRACT_PUBMED_18434152}}
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</StructureSection>
==About this Structure==
3CKR 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=3CKR OCA].
 
==Reference==
Synthesis, SAR, and X-ray structure of human BACE-1 inhibitors with cyclic urea derivatives., Park H, Min K, Kwak HS, Koo KD, Lim D, Seo SW, Choi JU, Platt B, Choi DY, Bioorg Med Chem Lett. 2008 May 1;18(9):2900-4. Epub 2008 Apr 8. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/18434152 18434152]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Memapsin 2]]
[[Category: Memapsin 2]]
[[Category: Single protein]]
[[Category: Min, K]]
[[Category: Min, K.]]
[[Category: Alternative splicing]]
[[Category: Alternative splicing]]
[[Category: Aspartyl protease]]
[[Category: Aspartyl protease]]
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[[Category: Transmembrane]]
[[Category: Transmembrane]]
[[Category: Zymogen]]
[[Category: Zymogen]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 00:58:28 2008''

Latest revision as of 10:29, 10 November 2021

Crystal structure of BACE-1 in complex with inhibitorCrystal structure of BACE-1 in complex with inhibitor

Structural highlights

3ckr is a 3 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
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

We describe synthesis and evaluation of a series of cyclic urea derivatives with hydroxylethylamine isostere. Modification of P3, P1, and P2' and combination of SAR display a >100-fold increase in potency with good cellular activity (IC(50)=0.15microM) relative to the previously reported compound 3.

Synthesis, SAR, and X-ray structure of human BACE-1 inhibitors with cyclic urea derivatives.,Park H, Min K, Kwak HS, Koo KD, Lim D, Seo SW, Choi JU, Platt B, Choi DY Bioorg Med Chem Lett. 2008 May 1;18(9):2900-4. Epub 2008 Apr 8. PMID:18434152[3]

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

See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ Park H, Min K, Kwak HS, Koo KD, Lim D, Seo SW, Choi JU, Platt B, Choi DY. Synthesis, SAR, and X-ray structure of human BACE-1 inhibitors with cyclic urea derivatives. Bioorg Med Chem Lett. 2008 May 1;18(9):2900-4. Epub 2008 Apr 8. PMID:18434152 doi:10.1016/j.bmcl.2008.03.081

3ckr, resolution 2.70Å

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