2v00: Difference between revisions

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File:2v00.jpg

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Ligands:

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Activity:

Endothiapepsin, with EC number 3.4.23.22

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save as pdb, mmCIF, xml

X-RAY CRYSTAL STRUCTURE OF ENDOTHIAPEPSIN COMPLEXED WITH COMPOUND 1

OverviewOverview

Fragment-based lead generation was applied to find novel small-molecule inhibitors of beta-secretase (BACE-1), a key target for the treatment of Alzheimer's disease. Fragment hits coming from a 1D NMR screen were characterized by BIAcore, and the most promising compounds were soaked into protein crystals to help the rational design of more potent hit analogues. Problems arising due to our inability to grow BACE-1 crystals at the biologically relevant pH at which the screen was run were overcome by using endothiapepsin as a surrogate aspartyl protease. Among others, we identified 6-substituted isocytosines as a novel warhead against BACE-1, and the accompanying paper in this journal describes how these were optimized to a lead series of nanomolar inhibitors.1.

About this StructureAbout this Structure

2V00 is a Single protein structure of sequence from Cryphonectria parasitica. Full crystallographic information is available from OCA.

ReferenceReference

Discovery of a novel warhead against beta-secretase through fragment-based lead generation., Geschwindner S, Olsson LL, Albert JS, Deinum J, Edwards PD, de Beer T, Folmer RH, J Med Chem. 2007 Nov 29;50(24):5903-11. Epub 2007 Nov 7. PMID:17985861

Page seeded by OCA on Thu Mar 20 18:41:46 2008

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

@@ Line 1: / Line 1: @@
-[[Image:2v00.jpg|left|200px]]<br /><applet load="2v00" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:2v00.jpg|left|200px]]
-caption="2v00, resolution 1.55&Aring;" />
-'''X-RAY CRYSTAL STRUCTURE OF ENDOTHIAPEPSIN COMPLEXED WITH COMPOUND 1'''<br />
+ {{Structure
+|PDB= 2v00 |SIZE=350|CAPTION= <scene name='initialview01'>2v00</scene>, resolution 1.55&Aring;
+|SITE= <scene name='pdbsite=AC1:Gol+Binding+Site+For+Chain+A'>AC1</scene>, <scene name='pdbsite=AC2:Gol+Binding+Site+For+Chain+A'>AC2</scene>, <scene name='pdbsite=AC3:Gol+Binding+Site+For+Chain+A'>AC3</scene>, <scene name='pdbsite=AC4:Act+Binding+Site+For+Chain+A'>AC4</scene>, <scene name='pdbsite=AC5:Act+Binding+Site+For+Chain+A'>AC5</scene> and <scene name='pdbsite=AC6:V15+Binding+Site+For+Chain+A'>AC6</scene>
+|LIGAND= <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=V15:'>V15</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>
+|ACTIVITY= [http://en.wikipedia.org/wiki/Endothiapepsin Endothiapepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.22 3.4.23.22]
+|GENE=
+}}
+'''X-RAY CRYSTAL STRUCTURE OF ENDOTHIAPEPSIN COMPLEXED WITH COMPOUND 1'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-V00 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Cryphonectria_parasitica Cryphonectria parasitica] with <scene name='pdbligand=ACT:'>ACT</scene>, <scene name='pdbligand=V15:'>V15</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Endothiapepsin Endothiapepsin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.23.22 3.4.23.22] Known structural/functional Sites: <scene name='pdbsite=AC1:Gol+Binding+Site+For+Chain+A'>AC1</scene>, <scene name='pdbsite=AC2:Gol+Binding+Site+For+Chain+A'>AC2</scene>, <scene name='pdbsite=AC3:Gol+Binding+Site+For+Chain+A'>AC3</scene>, <scene name='pdbsite=AC4:Act+Binding+Site+For+Chain+A'>AC4</scene>, <scene name='pdbsite=AC5:Act+Binding+Site+For+Chain+A'>AC5</scene> and <scene name='pdbsite=AC6:V15+Binding+Site+For+Chain+A'>AC6</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V00 OCA].
+V00 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Cryphonectria_parasitica Cryphonectria parasitica]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2V00 OCA].
 ==Reference==
-Discovery of a novel warhead against beta-secretase through fragment-based lead generation., Geschwindner S, Olsson LL, Albert JS, Deinum J, Edwards PD, de Beer T, Folmer RH, J Med Chem. 2007 Nov 29;50(24):5903-11. Epub 2007 Nov 7. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17985861 17985861]
+Discovery of a novel warhead against beta-secretase through fragment-based lead generation., Geschwindner S, Olsson LL, Albert JS, Deinum J, Edwards PD, de Beer T, Folmer RH, J Med Chem. 2007 Nov 29;50(24):5903-11. Epub 2007 Nov 7. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/17985861 17985861]
 [[Category: Cryphonectria parasitica]]
 [[Category: Endothiapepsin]]
@@ Line 37: / Line 46: @@
 [[Category: zymogen]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 18:51:59 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 18:41:46 2008''