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4BCY

Monomeric Human Cu,Zn Superoxide dismutase, mutation H43F

Summary for 4BCY
Entry DOI10.2210/pdb4bcy/pdb
Related4BCZ 4BD4
DescriptorSUPEROXIDE DISMUTASE [CU-ZN], COPPER (II) ION, ZINC ION, ... (6 entities in total)
Functional Keywordsoxidoreductase, disease mutation binding, protein folding, neurodegeneration, als
Biological sourceHOMO SAPIENS (HUMAN)
Total number of polymer chains1
Total formula weight16764.33
Authors
Awad, W.,Saraboji, K.,Danielsson, J.,Lang, L.,Kurnik, M.,Marklund, S.L.,Oliveberg, M.,Logan, D.T. (deposition date: 2012-10-03, release date: 2013-02-27, Last modification date: 2023-12-20)
Primary citationDanielsson, J.,Awad, W.,Saraboji, K.,Kurnik, M.,Lang, L.,Leinartaite, L.,Marklund, S.L.,Logan, D.T.,Oliveberg, M.
Global Structural Motions from the Strain of a Single Hydrogen Bond.
Proc.Natl.Acad.Sci.USA, 110:3829-, 2013
Cited by
PubMed Abstract: The origin and biological role of dynamic motions of folded enzymes is not yet fully understood. In this study, we examine the molecular determinants for the dynamic motions within the β-barrel of superoxide dismutase 1 (SOD1), which previously were implicated in allosteric regulation of protein maturation and also pathological misfolding in the neurodegenerative disease amyotrophic lateral sclerosis. Relaxation-dispersion NMR, hydrogen/deuterium exchange, and crystallographic data show that the dynamic motions are induced by the buried H43 side chain, which connects the backbones of the Cu ligand H120 and T39 by a hydrogen-bond linkage through the hydrophobic core. The functional role of this highly conserved H120-H43-T39 linkage is to strain H120 into the correct geometry for Cu binding. Upon elimination of the strain by mutation H43F, the apo protein relaxes through hydrogen-bond swapping into a more stable structure and the dynamic motions freeze out completely. At the same time, the holo protein becomes energetically penalized because the twisting back of H120 into Cu-bound geometry leads to burial of an unmatched backbone carbonyl group. The question then is whether this coupling between metal binding and global structural motions in the SOD1 molecule is an adverse side effect of evolving viable Cu coordination or plays a key role in allosteric regulation of biological function, or both?
PubMed: 23431167
DOI: 10.1073/PNAS.1217306110
PDB entries with the same primary citation
Experimental method
X-RAY DIFFRACTION (1.272 Å)
Structure validation

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