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.


2c3t

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:2c3t.gif|left|200px]]
+
{{Seed}}
 +
[[Image:2c3t.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_2c3t| PDB=2c3t | SCENE= }}
{{STRUCTURE_2c3t| PDB=2c3t | SCENE= }}
-
'''HUMAN GLUTATHIONE-S-TRANSFERASE T1-1, W234R MUTANT, APO FORM'''
+
===HUMAN GLUTATHIONE-S-TRANSFERASE T1-1, W234R MUTANT, APO FORM===
-
==Overview==
+
<!--
-
The crystal structures of wild-type human theta class glutathione-S-transferase (GST) T1-1 and its W234R mutant, where Trp234 was replaced by Arg, were solved both in the presence and absence of S-hexyl-glutathione. The W234R mutant was of interest due to its previously observed enhanced catalytic activity compared to the wild-type enzyme. GST T1-1 from rat and mouse naturally contain Arg in position 234, with correspondingly high catalytic efficiency. The overall structure of GST T1-1 is similar to that of GST T2-2, as expected from their 53% sequence identity at the protein level. Wild-type GST T1-1 has the side-chain of Trp234 occupying a significant portion of the active site. This bulky residue prevents efficient binding of both glutathione and hydrophobic substrates through steric hindrance. The wild-type GST T1-1 crystal structure, obtained from co-crystallization experiments with glutathione and its derivatives, showed no electron density for the glutathione ligand. However, the structure of GST T1-1 mutant W234R showed clear electron density for S-hexyl-glutathione after co-crystallization. In contrast to Trp234 in the wild-type structure, the side-chain of Arg234 in the mutant does not occupy any part of the substrate-binding site. Instead, Arg234 is pointing in a different direction and, in addition, interacts with the carboxylate group of glutathione. These findings explain our earlier observation that the W234R mutant has a markedly improved catalytic activity with most substrates tested to date compared to the wild-type enzyme. GST T1-1 catalyzes detoxication reactions as well as reactions that result in toxic products, and our findings therefore suggest that humans have gained an evolutionary advantage by a partially disabled active site.
+
The line below this paragraph, {{ABSTRACT_PUBMED_16298388}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 16298388 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_16298388}}
==About this Structure==
==About this Structure==
Line 34: Line 38:
[[Category: T1-1]]
[[Category: T1-1]]
[[Category: Transferase]]
[[Category: Transferase]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 21:12:27 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 20:12:40 2008''

Revision as of 17:12, 27 July 2008

Image:2c3t.png

Template:STRUCTURE 2c3t

HUMAN GLUTATHIONE-S-TRANSFERASE T1-1, W234R MUTANT, APO FORM

Template:ABSTRACT PUBMED 16298388

About this Structure

2C3T is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural basis of the suppressed catalytic activity of wild-type human glutathione transferase T1-1 compared to its W234R mutant., Tars K, Larsson AK, Shokeer A, Olin B, Mannervik B, Kleywegt GJ, J Mol Biol. 2006 Jan 6;355(1):96-105. Epub 2005 Nov 8. PMID:16298388

Page seeded by OCA on Sun Jul 27 20:12:40 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2c3t"
Personal tools