1ms6: Difference between revisions

Revision as of 01:39, 3 May 2008

Dipeptide Nitrile Inhibitor Bound to Cathepsin S.

OverviewOverview

The specificity of the immune response relies on processing of foreign proteins and presentation of antigenic peptides at the cell surface. Inhibition of antigen presentation, and the subsequent activation of T-cells, should, in theory, modulate the immune response. The cysteine protease Cathepsin S performs a fundamental step in antigen presentation and therefore represents an attractive target for inhibition. Herein, we report a series of potent and reversible Cathepsin S inhibitors based on dipeptide nitriles. These inhibitors show nanomolar inhibition of the target enzyme as well as cellular potency in a human B cell line. The first X-ray crystal structure of a reversible inhibitor cocrystallized with Cathepsin S is also reported.

About this StructureAbout this Structure

1MS6 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

Design and synthesis of dipeptide nitriles as reversible and potent Cathepsin S inhibitors., Ward YD, Thomson DS, Frye LL, Cywin CL, Morwick T, Emmanuel MJ, Zindell R, McNeil D, Bekkali Y, Girardot M, Hrapchak M, DeTuri M, Crane K, White D, Pav S, Wang Y, Hao MH, Grygon CA, Labadia ME, Freeman DM, Davidson W, Hopkins JL, Brown ML, Spero DM, J Med Chem. 2002 Dec 5;45(25):5471-82. PMID:12459015 Page seeded by OCA on Sat May 3 01:39:32 2008

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OCA

@@ Line 1: / Line 1: @@
 [[Image:1ms6.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1ms6 |SIZE=350|CAPTION= <scene name='initialview01'>1ms6</scene>, resolution 1.90&Aring;
+The line below this paragraph, containing "STRUCTURE_1ms6", creates the "Structure Box" on the page.
-|SITE=
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=BLN:MORPHOLINE-4-CARBOXYLIC+ACID+[1S-(2-BENZYLOXY-1R-CYANO-ETHYLCARBAMOYL)-3-METHYL-BUTYL]AMIDE'>BLN</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Cathepsin_S Cathepsin S], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.22.27 3.4.22.27] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1ms6|  PDB=1ms6  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1ms6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ms6 OCA], [http://www.ebi.ac.uk/pdbsum/1ms6 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1ms6 RCSB]</span>
-}}
 '''Dipeptide Nitrile Inhibitor Bound to Cathepsin S.'''
@@ Line 50: / Line 47: @@
 [[Category: White, D.]]
 [[Category: Zindell, R.]]
-[[Category: cathepsin]]
+[[Category: Cathepsin]]
-[[Category: hydrolase]]
+[[Category: Hydrolase]]
-[[Category: protease]]
+[[Category: Protease]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 01:39:32 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 22:20:27 2008''