2gbt

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{{STRUCTURE_2gbt| PDB=2gbt | SCENE= }}
{{STRUCTURE_2gbt| PDB=2gbt | SCENE= }}
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'''C6A/C111A CuZn Superoxide dismutase'''
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===C6A/C111A CuZn Superoxide dismutase===
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==Overview==
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The gain of neurotoxic function in amyotrophic lateral sclerosis (ALS) has been linked to misfolding of the homodimeric enzyme Cu/Zn superoxide dismutase (SOD). Here, we present the crystal structure of fully cysteine-depleted human SOD (SOD(CallA)), representing a reduced, marginally stable intermediate on the folding pathway in vivo that has also been implicated as neurotoxic precursor state. A hallmark of this species is that it fails to dimerize and becomes trapped as a monomer in the absence of the active-site metals. The crystallographic data show that removal of the C57-C146 disulphide bond sets free the interface loop IV in the apo protein, whereas the same loop remains unaffected in the holo protein. Thus, the low dimerisation propensity of disulphide-reduced apoSOD seems to be of entropic origin due to increased loop flexibility in the monomeric state: in the disulphide-reduced holo protein this gain in configurational entropy upon splitting of the dimer interface is reduced by the metal coordination.
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{{ABSTRACT_PUBMED_17070542}}
==Disease==
==Disease==
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[[Category: Human cu/zn superoxide dismutase]]
[[Category: Human cu/zn superoxide dismutase]]
[[Category: Oxidoreductase]]
[[Category: Oxidoreductase]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 14:43:04 2008''

Revision as of 11:43, 27 July 2008

Image:2gbt.png

Template:STRUCTURE 2gbt

Contents

C6A/C111A CuZn Superoxide dismutase

Template:ABSTRACT PUBMED 17070542

Disease

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

About this Structure

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

Reference

The coupling between disulphide status, metallation and dimer interface strength in Cu/Zn superoxide dismutase., Hornberg A, Logan DT, Marklund SL, Oliveberg M, J Mol Biol. 2007 Jan 12;365(2):333-42. Epub 2006 Sep 23. PMID:17070542

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