This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.


2hxz

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:2hxz.jpg|left|200px]]
+
{{Seed}}
 +
[[Image:2hxz.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_2hxz| PDB=2hxz | SCENE= }}
{{STRUCTURE_2hxz| PDB=2hxz | SCENE= }}
-
'''Crystal Structure of Cathepsin S in complex with a Nonpeptidic Inhibitor (Hexagonal spacegroup)'''
+
===Crystal Structure of Cathepsin S in complex with a Nonpeptidic Inhibitor (Hexagonal spacegroup)===
-
==Overview==
+
<!--
-
The substrate activity screening method, a substrate-based fragment identification and optimization method for the development of enzyme inhibitors, was previously applied to cathepsin S to obtain low nanomolar 1,4-disubstituted-1,2,3-triazole-based aldehyde inhibitors (Wood, W. J. L.; Patterson, A. W.; Tsuruoka, H.; Jain, R. K.; Ellman, J. A. J. Am. Chem. Soc. 2005, 127, 15521-15527). Replacement of the metabolically labile aldehyde pharmacophore with the nitrile pharmacophore provided inhibitors with moderate potency for cathepsin S. The inhibitors showed good selectivity over cathepsins B and L but no selectivity over cathepsin K. X-ray structures of two crystal forms (1.5 and 1.9 A) of a complex between cathepsin S and a triazole inhibitor incorporating a chloromethyl ketone pharmacophore guided the design of triazole substrates with increased cleavage efficiency and selectivity for cathepsin S over cathepsins B, L, and K. Conversion of select substrates to nitrile inhibitors yielded a low molecular weight (414 Da) and potent (15 nM) cathepsin S inhibitor that showed &gt;1000-fold selectivity over cathepsins B, L, and K.
+
The line below this paragraph, {{ABSTRACT_PUBMED_17034136}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 17034136 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_17034136}}
==About this Structure==
==About this Structure==
Line 33: Line 37:
[[Category: Nonpeptidic]]
[[Category: Nonpeptidic]]
[[Category: Substrate activity screening]]
[[Category: Substrate activity screening]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 06:51:03 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 05:34:20 2008''

Revision as of 02:34, 28 July 2008

Image:2hxz.png

Template:STRUCTURE 2hxz

Crystal Structure of Cathepsin S in complex with a Nonpeptidic Inhibitor (Hexagonal spacegroup)

Template:ABSTRACT PUBMED 17034136

About this Structure

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

Reference

Identification of selective, nonpeptidic nitrile inhibitors of cathepsin s using the substrate activity screening method., Patterson AW, Wood WJ, Hornsby M, Lesley S, Spraggon G, Ellman JA, J Med Chem. 2006 Oct 19;49(21):6298-307. PMID:17034136

Page seeded by OCA on Mon Jul 28 05:34:20 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

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