4BD4

Monomeric Human Cu,Zn Superoxide dismutase, loops IV and VII deleted, apo form, mutant H43F

Summary for 4BD4

• Entry DOI: 10.2210/pdb4bd4/pdb
• Related: 1AZV 1BA9 1DSW 1FUN 1HL4 1HL5 1KMG 1L3N 1MFM 1N18 1N19 1OEZ 1OZT 1OZU 1P1V 1PTZ 1PU0 1RK7 1SOS 1SPD 1UXL 1UXM 2AF2 2C9S 2C9U 2C9V 2V0A 2VR6 2VR7 2VR8 2WKO 2WYT 2WYZ 2WZ0 2WZ5 2WZ6 2XJK 2XJL 4A7G 4A7Q 4A7R 4A7S 4A7T 4A7U 4A7V 4B3E 4BCY 4BCZ
• Descriptor: SUPEROXIDE DISMUTASE [CU-ZN], GLYCEROL (3 entities in total)
• Functional Keywords: oxidoreductase, cu/zn sod1, monomeric mutant, disease mutation, metal binding, neurodegeneration, als
• Biological source: HOMO SAPIENS (HUMAN)
• Cellular location: Cytoplasm : P00441
• Total number of polymer chains: 9
• Total formula weight: 99362.23

Authors

Awad, W.,Saraboji, K.,Danielsson, J.,Lang, L.,Kurnik, M.,Marklund, S.L.,Oliveberg, M.,Logan, D.T. (deposition date: 2012-10-04, release date: 2013-02-27, Last modification date: 2023-12-20)

Primary citation

Danielsson, 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

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

Experimental method

X-RAY DIFFRACTION (2.78 Å)