Database accession: MF2100014
Name: Superoxide dismutase (SOD)
PDB ID: 2c9v
Experimental method: X-ray (1.07 Å)
Assembly: Homodimer
Source organism: Homo sapiens
Primary publication of the structure:
Strange RW, Antonyuk SV, Hough MA, Doucette PA, Valentine JS, Hasnain SS
Variable metallation of human superoxide dismutase: atomic resolution crystal structures of Cu-Zn, Zn-Zn and as-isolated wild-type enzymes.
(2006) J. Mol. Biol. 356: 1152-62
PMID: 16406071
Abstract:
Human Cu-Zn superoxide dismutase (SOD1) protects cells from the effects of oxidative stress. Mutations in SOD1 are linked to the familial form of amyotrophic lateral sclerosis. Several hypotheses for their toxicity involve the mis-metallation of the enzyme. We present atomic-resolution crystal structures and biophysical data for human SOD1 in three metallation states: Zn-Zn, Cu-Zn and as-isolated. These data represent the first atomic-resolution structures for human SOD1, the first structure of a reduced SOD1, and the first structure of a fully Zn-substituted SOD1 enzyme. Recombinantly expressed as-isolated SOD1 contains a mixture of Zn and Cu at the Cu-binding site. The Zn-Zn structure appears to be at least as stable as the correctly (Cu-Zn) metallated enzyme. These data raise the possibility that in a cellular environment with low availability of free copper, Zn-Zn may be the preferred metallation state of SOD1 prior to its interaction with the copper chaperone.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
copper ion binding copper ion binding
identical protein binding identical protein binding
protein phosphatase 2B binding protein phosphatase 2B binding
protein-folding chaperone binding protein-folding chaperone binding
small GTPase binding small GTPase binding
superoxide dismutase activity superoxide dismutase activity
zinc ion binding zinc ion binding
Biological process:
action potential initiation action potential initiation
anterograde axonal transport anterograde axonal transport
apoptotic process apoptotic process
auditory receptor cell stereocilium organization auditory receptor cell stereocilium organization
determination of adult lifespan determination of adult lifespan
ectopic germ cell programmed cell death ectopic germ cell programmed cell death
embryo implantation embryo implantation
gene expression gene expression
glutathione metabolic process glutathione metabolic process
heart contraction heart contraction
hydrogen peroxide biosynthetic process hydrogen peroxide biosynthetic process
intracellular iron ion homeostasis intracellular iron ion homeostasis
locomotory behavior locomotory behavior
muscle cell cellular homeostasis muscle cell cellular homeostasis
myeloid cell homeostasis myeloid cell homeostasis
negative regulation of cholesterol biosynthetic process negative regulation of cholesterol biosynthetic process
negative regulation of developmental process negative regulation of developmental process
negative regulation of inflammatory response negative regulation of inflammatory response
negative regulation of neuron apoptotic process negative regulation of neuron apoptotic process
negative regulation of reproductive process negative regulation of reproductive process
neurofilament cytoskeleton organization neurofilament cytoskeleton organization
neuronal action potential neuronal action potential
ovarian follicle development ovarian follicle development
peripheral nervous system myelin maintenance peripheral nervous system myelin maintenance
placenta development placenta development
positive regulation of apoptotic process positive regulation of apoptotic process
positive regulation of catalytic activity positive regulation of catalytic activity
positive regulation of cytokine production positive regulation of cytokine production
positive regulation of MAPK cascade positive regulation of MAPK cascade
positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
positive regulation of phagocytosis positive regulation of phagocytosis
positive regulation of superoxide anion generation positive regulation of superoxide anion generation
reactive oxygen species metabolic process reactive oxygen species metabolic process
regulation of blood pressure regulation of blood pressure
regulation of GTPase activity regulation of GTPase activity
regulation of mitochondrial membrane potential regulation of mitochondrial membrane potential
regulation of multicellular organism growth regulation of multicellular organism growth
regulation of organ growth regulation of organ growth
regulation of protein kinase activity regulation of protein kinase activity
regulation of T cell differentiation in thymus regulation of T cell differentiation in thymus
relaxation of vascular associated smooth muscle relaxation of vascular associated smooth muscle
removal of superoxide radicals removal of superoxide radicals
response to axon injury response to axon injury
response to ethanol response to ethanol
response to heat response to heat
response to hydrogen peroxide response to hydrogen peroxide
response to organic substance obsolete response to organic substance
response to superoxide response to superoxide
response to xenobiotic stimulus response to xenobiotic stimulus
retina homeostasis retina homeostasis
retrograde axonal transport retrograde axonal transport
sensory perception of sound sensory perception of sound
spermatogenesis spermatogenesis
superoxide anion generation superoxide anion generation
superoxide metabolic process superoxide metabolic process
thymus development thymus development
transmission of nerve impulse transmission of nerve impulse
Cellular component:
axon cytoplasm axon cytoplasm
cytoplasm cytoplasm
cytoplasmic vesicle cytoplasmic vesicle
cytosol cytosol
dendrite cytoplasm dendrite cytoplasm
extracellular exosome extracellular exosome
extracellular region extracellular region
extracellular space extracellular space
mitochondrial intermembrane space mitochondrial intermembrane space
mitochondrial matrix mitochondrial matrix
mitochondrion mitochondrion
neuronal cell body neuronal cell body
nucleoplasm nucleoplasm
nucleus nucleus
peroxisome peroxisome
protein-containing complex protein-containing complex
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: A, F
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 1
Name: Superoxide dismutase [Cu-Zn]
Source organism: Homo sapiens
Length: 154 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMATKAVCVLKGDGPVQGIINFEQKESNGPVKVWGSIKGLTEGLHGFHVHEFGDNTAGCTSAGPHFNPLSRKHGGPKDEERHVGDLGNVTADKDGVADVSIEDSVISLSGDHCIIGRTLVVHEKADDLGKGGNEESTKTGNAGSRLACGVIGIAQ
UniProtKB AC: P00441 (positions: 2-154)
Coverage: 99%
Name: Superoxide dismutase [Cu-Zn]
Source organism: Homo sapiens
Length: 154 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMATKAVCVLKGDGPVQGIINFEQKESNGPVKVWGSIKGLTEGLHGFHVHEFGDNTAGCTSAGPHFNPLSRKHGGPKDEERHVGDLGNVTADKDGVADVSIEDSVISLSGDHCIIGRTLVVHEKADDLGKGGNEESTKTGNAGSRLACGVIGIAQ
UniProtKB AC: P00441 (positions: 2-154)
Coverage: 99%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: -
Evidence level: Direct evidence
Evidence coverage: The full structure participates in mutual synergistic folding.
Complex Evidence:
CD measurements and a global analysis decomposition of the time-resolved fluorescence decay over denaturant concentration shows the presence of an intermediate in the unfolding of human SOD by guanidinium hydrochloride. Considering previous measurements of partially denatured HSOD as a function of protein concentration (PMID:1510915), these results strongly suggest that the unfolding intermediate is a monomer that displays a molten globule state (PMID:8298055).
Chain A:
N/A
Chain F:
N/A
Surface and contacts features:
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). No related structure was found in the MFIB database.
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