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.


2r27

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Line 1: Line 1:
-
[[Image:2r27.jpg|left|200px]]
+
{{Seed}}
 +
[[Image:2r27.png|left|200px]]
<!--
<!--
Line 9: Line 10:
{{STRUCTURE_2r27| PDB=2r27 | SCENE= }}
{{STRUCTURE_2r27| PDB=2r27 | SCENE= }}
-
'''Constitutively zinc-deficient mutant of human superoxide dismutase (SOD), C6A, H80S, H83S, C111S'''
+
===Constitutively zinc-deficient mutant of human superoxide dismutase (SOD), C6A, H80S, H83S, C111S===
-
==Overview==
+
<!--
-
Over 130 mutations to copper, zinc superoxide dismutase (SOD) are implicated in the selective death of motor neurons found in 25% of patients with familial amyotrophic lateral sclerosis (ALS). Despite their widespread distribution, ALS mutations appear positioned to cause structural and misfolding defects. Such defects decrease SOD's affinity for zinc, and loss of zinc from SOD is sufficient to induce apoptosis in motor neurons in vitro. To examine the importance of the zinc site in the structure and pathogenesis of human SOD, we determined the 2.0-A-resolution crystal structure of a designed zinc-deficient human SOD, in which two zinc-binding ligands have been mutated to hydrogen-bonding serine residues. This structure revealed a 9 degrees twist of the subunits, which opens the SOD dimer interface and represents the largest intersubunit rotational shift observed for a human SOD variant. Furthermore, the electrostatic loop and zinc-binding subloop were partly disordered, the catalytically important Arg143 was rotated away from the active site, and the normally rigid intramolecular Cys57-Cys146 disulfide bridge assumed two conformations. Together, these changes allow small molecules greater access to the catalytic copper, consistent with the observed increased redox activity of zinc-deficient SOD. Moreover, the dimer interface is weakened and the Cys57-Cys146 disulfide is more labile, as demonstrated by the increased aggregation of zinc-deficient SOD in the presence of a thiol reductant. However, equimolar Cu,Zn SOD rapidly forms heterodimers with zinc-deficient SOD (t1/2 approximately 15 min) and prevents aggregation. The stabilization of zinc-deficient SOD as a heterodimer with Cu,Zn SOD may contribute to the dominant inheritance of ALS mutations. These results have general implications for the importance of framework stability on normal metalloenzyme function and specific implications for the role of zinc ion in the fatal neuropathology associated with SOD mutations.
+
The line below this paragraph, {{ABSTRACT_PUBMED_17888947}}, adds the Publication Abstract to the page
 +
(as it appears on PubMed at http://www.pubmed.gov), where 17888947 is the PubMed ID number.
 +
-->
 +
{{ABSTRACT_PUBMED_17888947}}
==Disease==
==Disease==
Line 42: Line 46:
[[Category: Oxidoreductase]]
[[Category: Oxidoreductase]]
[[Category: Zinc]]
[[Category: Zinc]]
-
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 16:06:34 2008''
+
 
 +
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Tue Jul 29 02:32:12 2008''

Revision as of 23:32, 28 July 2008

Image:2r27.png

Template:STRUCTURE 2r27

Contents

Constitutively zinc-deficient mutant of human superoxide dismutase (SOD), C6A, H80S, H83S, C111S

Template:ABSTRACT PUBMED 17888947

Disease

Known disease associated with this structure: Amyotrophic lateral sclerosis, due to SOD1 deficiency OMIM:[147450]

About this Structure

2R27 is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Structural characterization of zinc-deficient human superoxide dismutase and implications for ALS., Roberts BR, Tainer JA, Getzoff ED, Malencik DA, Anderson SR, Bomben VC, Meyers KR, Karplus PA, Beckman JS, J Mol Biol. 2007 Nov 2;373(4):877-90. Epub 2007 Aug 2. PMID:17888947

Page seeded by OCA on Tue Jul 29 02:32:12 2008

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2r27"
Personal tools