2GBU

C6A/C111A/C57A/C146A apo CuZn Superoxide dismutase

Summary for 2GBU

• Entry DOI: 10.2210/pdb2gbu/pdb
• Related: 1HL4 2GBT 2GBV
• Descriptor: Superoxide dismutase [Cu-Zn] (2 entities in total)
• Functional Keywords: oxidoreductase, human cu/zn superoxide dismutase, cystein-free
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm : P00441
• Total number of polymer chains: 4
• Total formula weight: 62797.20

Authors

Hornberg, A.,Logan, D.T.,Marklund, S.L.,Oliveberg, M. (deposition date: 2006-03-11, release date: 2007-01-02, Last modification date: 2023-10-25)

Primary citation

Hornberg, A.,Logan, D.T.,Marklund, S.L.,Oliveberg, M.
The Coupling between Disulphide Status, Metallation and Dimer Interface Strength in Cu/Zn Superoxide Dismutase
J.Mol.Biol., 365:333-342, 2007

PubMed Abstract: 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.

PubMed: 17070542
DOI: 10.1016/j.jmb.2006.09.048

Experimental method

X-RAY DIFFRACTION (2 Å)