1ms6: Difference between revisions

← Older edit Newer edit →

Revision as of 13:47, 20 March 2008

File:1ms6.gif

, resolution 1.90Å

Ligands:

Activity:

Cathepsin S, with EC number 3.4.22.27

Coordinates:

save as pdb, mmCIF, xml

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 Thu Mar 20 12:47:33 2008

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

OCA

@@ Line 1: / Line 1: @@
-[[Image:1ms6.gif|left|200px]]<br /><applet load="1ms6" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:1ms6.gif|left|200px]]
-caption="1ms6, resolution 1.90&Aring;" />
-'''Dipeptide Nitrile Inhibitor Bound to Cathepsin S.'''<br />
+ {{Structure
+|PDB= 1ms6 |SIZE=350|CAPTION= <scene name='initialview01'>1ms6</scene>, resolution 1.90&Aring;
+|SITE=
+|LIGAND= <scene name='pdbligand=BLN:MORPHOLINE-4-CARBOXYLIC ACID [1S-(2-BENZYLOXY-1R-CYANO-ETHYLCARBAMOYL)-3-METHYL-BUTYL]AMIDE'>BLN</scene>
+|ACTIVITY= [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]
+|GENE=
+}}
+'''Dipeptide Nitrile Inhibitor Bound to Cathepsin S.'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-MS6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=BLN:'>BLN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1MS6 OCA].
+MS6 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=1MS6 OCA].
 ==Reference==
-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:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12459015 12459015]
+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:[http://www.ncbi.nlm.nih.gov/pubmed/12459015 12459015]
 [[Category: Cathepsin S]]
 [[Category: Homo sapiens]]
@@ Line 43: / Line 52: @@
 [[Category: protease]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:58:32 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 12:47:33 2008''