2gbv
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| , resolution 2.000Å | |||||||
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| Ligands: | , | ||||||
| Gene: | SOD1 (Homo sapiens) | ||||||
| Activity: | Superoxide dismutase, with EC number 1.15.1.1 | ||||||
| Related: | 1HL4, 1N18, 2GBT, 2GBU
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| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
C6A/C111A/C57A/C146A holo CuZn Superoxide dismutase
OverviewOverview
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.
DiseaseDisease
Known disease associated with this structure: Amyotrophic lateral sclerosis, due to SOD1 deficiency OMIM:[147450]
About this StructureAbout this Structure
2GBV is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
ReferenceReference
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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