2va7

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:2va7.jpg|left|200px]]
+
{{Seed}}
 +
[[Image:2va7.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_2va7| PDB=2va7 | SCENE= }}
{{STRUCTURE_2va7| PDB=2va7 | SCENE= }}
-
'''X-RAY CRYSTAL STRUCTURE OF BETA SECRETASE COMPLEXED WITH COMPOUND 27'''
+
===X-RAY CRYSTAL STRUCTURE OF BETA SECRETASE COMPLEXED WITH COMPOUND 27===
-
==Overview==
+
<!--
-
Fragment-based lead generation has led to the discovery of a novel series of cyclic amidine-based inhibitors of beta-secretase (BACE-1). Initial fragment hits with an isocytosine core having millimolar potency were identified via NMR affinity screening. Structure-guided evolution of these fragments using X-ray crystallography together with potency determination using surface plasmon resonance and functional enzyme inhibition assays afforded micromolar inhibitors. Similarity searching around the isocytosine core led to the identification of a related series of inhibitors, the dihydroisocytosines. By leveraging the knowledge of the ligand-BACE-1 recognition features generated from the isocytosines, the dihydroisocytosines were efficiently optimized to submicromolar potency. Compound 29, with an IC50 of 80 nM, a ligand efficiency of 0.37, and cellular activity of 470 nM, emerged as the lead structure for future optimization.
+
The line below this paragraph, {{ABSTRACT_PUBMED_17985862}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 17985862 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_17985862}}
==About this Structure==
==About this Structure==
Line 58: Line 62:
[[Category: Transmembrane]]
[[Category: Transmembrane]]
[[Category: Zymogen]]
[[Category: Zymogen]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 18:28:52 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 23:35:41 2008''

Revision as of 20:35, 28 July 2008

Image:2va7.png

Template:STRUCTURE 2va7

X-RAY CRYSTAL STRUCTURE OF BETA SECRETASE COMPLEXED WITH COMPOUND 27

Template:ABSTRACT PUBMED 17985862

About this Structure

2VA7 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Application of fragment-based lead generation to the discovery of novel, cyclic amidine beta-secretase inhibitors with nanomolar potency, cellular activity, and high ligand efficiency., Edwards PD, Albert JS, Sylvester M, Aharony D, Andisik D, Callaghan O, Campbell JB, Carr RA, Chessari G, Congreve M, Frederickson M, Folmer RH, Geschwindner S, Koether G, Kolmodin K, Krumrine J, Mauger RC, Murray CW, Olsson LL, Patel S, Spear N, Tian G, J Med Chem. 2007 Nov 29;50(24):5912-25. Epub 2007 Nov 7. PMID:17985862

Page seeded by OCA on Mon Jul 28 23:35:41 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2va7"
Personal tools