CODSWALLOP

Superoxide dismutase [Cu-Zn]

Homo sapiens · seed P00441 · 154 aa · family defined as ≥30% identity to that seed · compiled 07 October 2026

CATH and SCOP identifiers come from the RCSB's own structure annotations, which the Domains panel already reads, so these are looked up rather than guessed at.

252Entries 264Entities 142Constructs 36Organisms 229Ligand-bound
0.98 ÅBest res.
1.90 ÅMedian res.

Every figure here is counted over the whole family rather than quoted from one entry.

The reference structure

1HL4, the structure every other member of this family is superposed onto. Rendered by the RCSB and embedded here: the live app shows an interactive viewport, which a document that fetches nothing cannot.

Rendered structure of 1HL4
1HL4 at the RCSB · open it in the 3D viewer

Which residues anyone has ever seen

How many of this family's constructs contain each residue of the seed. A trough is a stretch nobody has put in a construct, which is a construct-design answer rather than a disorder one.

177154264 constructs

Constructs, most-used first

142 distinct constructs across 252 entries. 236 polymer entities differ from the UniProt canonical sequence in some way, 11 carry a recognised expression tag and 0 carry a fusion partner.

"Differs from canonical" is not the same as "engineered". The canonical sequence is the full gene product, so a secreted protein whose structures all start after its signal peptide counts every one of them as different: lysozyme's most-used construct, residues 19–147 on 1,239 entities, is simply the mature protein. Read the construct column below for what was actually done, rather than this count.

EntitiesLengthBest (Å)Best entryWhat was made
23 153 1.07 2C9V residues 2-154
17 151 1.45 2ZOW residues 2-152
14 153 1.25 6Z3V residues 2-154; A5V
8 153 0.98 4A7U residues 2-154; I114T
8 154 1.67 8CCX matches the canonical sequence
6 153 1.35 7T8G residues 2-154; G94A
6 153 1.55 1JCV residues 2-154
6 154 1.80 3PU7 residues 64-217
4 153 1.00 2WYT residues 2-154; L39V
4 153 1.02 1MFM residues 2-154; C7A, F51E, G52E +2 more
4 153 2.00 6FOI residues 2-154; C58A, C147A
3 152 1.15 1Q0E matches the canonical sequence
3 153 1.30 2VR6 residues 2-154; G86R
3 153 1.40 7WX0 E40K, E51G, X53N
3 153 1.75 3K91 residues 2-154; H47R, H49Q
3 153 residues 2-154; C7A, C112S
3 154 1.97 2WKO G94A
3 165 1.60 6D52 His6; residues 21-177
3 180 1.90 5YTO His6; TEV site
2 110 residues 2-154; 3 internal deletions; C7A, H47W, E50G +4 more
2 152 0.99 3F7L residues 2-153
2 153 1.41 7B4O no UniProt reference for this entity, so it cannot be diffed against a canonical sequence
2 153 2.00 2GBU residues 2-154; C7A, C58A, C112A +1 more
2 153 2.15 1OEZ residues 2-154; H47R
2 153 2.20 4MCM residues 2-154; C58S

Showing the 25 most-used of 142.

Positions people deliberately mutate

Columns where the wild-type residue still dominates but a real minority carries something else, which is a different question from "what varies across species".

C112S 51% R70K 43% N20H 42% W33T 42% D97I 41% V104L 41% K37T 40% I18T 40% K31V 39% A56N 39% A124P 39% N27G 36% E101V 36% C7A 35% D110E 34% L43D 33% S99D 32% Q154K 32% S103P 32% H111Y 32% T3V 30% G28D 30% S35E 29% K76T 29% L118M 28% E50Q 28% L68F 28% K92A 28% E79V 28% S69K 28%

What it assembles into

Oligomeric stateChainsEntriesShare
dimeric2 199 79.0%
monomeric1 28 11.1%
tetrameric4 8 3.2%
trimeric3 8 3.2%
hexameric6 5 2.0%
24-meric24 2 0.8%
octameric8 1 0.4%
dodecameric12 1 0.4%

176 entries have the depositor's assembly corroborated by PISA, 71 carry the depositor's word alone and 5 were assigned by PISA where the depositor gave none. The middle figure is not a disagreement: PISA may have returned nothing or never run. 12 entries carry more than one assembly with different chain counts, so they have no single answer to quote: 1DO5, 1JK9, 1TO5, 1XTL, 1XTM, 2AQN, 2AQP, 2AQQ, 2AQR, 2AQT, 3HFF, 7FB9.

Domain architecture

Every source's own domains on the seed axis, one row each. They are not merged: Pfam, CATH, SCOP and InterPro disagree about boundaries, and a merged track would state a consensus none of them gave.

CATHSuperoxide dismutase, copp3.30.70.100SCOP2BCu,Zn superoxide dismutaseCu,Zn superoxide dismutaseCu,Zn superoxide dismutaseCu,Zn superoxide dismutaseCu,Zn superoxide dismutaseCu,Zn superoxide dismutaseCu,Zn superoxide dismutaseCu,Zn superoxide dismutaseCu,Zn superoxide dismutase177154
DomainSourceSpan (seed)Chains
Superoxide dismutase, copper/zinc binding domainCATH 2.60.40.200 2–154 185
3.30.70.100CATH 16–83 2
Cu,Zn superoxide dismutase-likeSCOP2B 8055253 2–154 118
Cu,Zn superoxide dismutase-likeSCOP2B 8055251 2–152 27
Cu,Zn superoxide dismutase-likeSCOP2B 8055259 4–154 11
Cu,Zn superoxide dismutase-likeSCOP2B 8062177 5–154 5
Cu,Zn superoxide dismutase-likeSCOP2B 8062205 24–154 2
Cu,Zn superoxide dismutase-likeSCOP2B 8062209 34–154 3
Cu,Zn superoxide dismutase-likeSCOP2B 8055265 37–154 2
Cu,Zn superoxide dismutase-likeSCOP2B 8062203 49–154 2
Cu,Zn superoxide dismutase-likeSCOP2B 8055277 81–154 4

What binds it

ZN ZN205 entries CU CU130 entries 9JT 9JT4 entries HEM HEM3 entries S4P S4P3 entries CPT CPT2 entries ACE ACE2 entries PS5 PS52 entries 5FW 5FW2 entries LQW LQW2 entries Q8H Q8H2 entries Q8E Q8E2 entries
ComponentClassNameEntriesBest (Å)
ZNcofactor Zinc Ion 205 0.98
CUcofactor Copper (Ii) Ion 130 0.98
SO4ion Sulfate Ion 72 0.98
GOLcryoprotectant Glycerol 25 1.25
CU1ion Copper (I) Ion 23 0.99
ACTcryoprotectant Acetate Ion 19 0.98
CLion Chloride Ion 15 1.00
DMScryoprotectant Dimethyl Sulfoxide 8 1.65
CAion Calcium Ion 7 1.80
NAion Sodium Ion 6 0.99
SCNion Thiocyanate Ion 5 1.30
AZIion Azide Ion 4 1.55
MLIbuffer Malonate Ion 4 1.55
9JTligand N-Phenyl-2-Selanylbenzamide 4 1.40
HEMcofactor Protoporphyrin Ix Containing Fe 3 1.50
EDOcryoprotectant 1,2-Ethanediol 3 1.30
MESbuffer 2-(N-Morpholino)-Ethanesulfonic Acid 3 1.45
S4Pligand Dihydrogen Tetrasulfide 3 1.90
PO4ion Phosphate Ion 2 1.35
CDion Cadmium Ion 2 1.02

How it crystallises

Parsed from the free text 203 depositors typed into _exptl_crystal_grow.pdbx_details, out of 215 entries that recorded anything at all. Median pH 6.5 (range 3.8 to 9.0).

Precipitants

PEG × Ammonium sulfate × Sodium chloride × Sodium malonate × Sodium citrate × Magnesium chloride × MPD × Lithium sulfate × Isopropanol × Dioxane × PEG (unspecified) × Jeffamine × Calcium chloride ×

Buffers

Sodium acetate × Tris × MES × HEPES × Citrate × Sodium cacodylate × Bis-Tris × Bis-Tris propane × Imidazole × Glycine × Phosphate ×

Which entries to trust

251 entries carry a wwPDB validation report: 124 clean, 84 worth a check and 43 with something to explain. Median clashscore 5.32, median RSRZ outliers 3.05%, median R-free minus R-work 0.039. 229 have released structure factors.

Across species

OrganismEntriesBest (Å)Ligand-boundSeed covered
Homo sapiens150 0.98 130 100%
Bos taurus25 1.15 28 100%
Saccharomyces cerevisiae11 1.35 11 97%
Canis lupus familiaris8 1.40 5 100%
Neisseria meningitidis6 1.30 6 82%
Solanum lycopersicum6 1.80 5 97%
Bombyx mori4 1.80 4 100%
Salmonella enterica subsp. enterica serovar Typhimurium3 1.70 3 75%
Alvinella pompejana2 0.99 2 98%
Caenorhabditis elegans2 1.10 1 99%
Bacteroidetes bacterium GWA2_30_72 1.41 2 97%
[Haemophilus] ducreyi2 1.50 2 73%

Seed sequence

154 residues, numbered every ten. Every identity figure in this document is measured against this sequence.

active or binding site modified residue or glycosylation disulphide cysteine transmembrane or signal the 15 most-substituted positions

1MATKAVCVLK GDGPVQGIIN FEQKESNGPV KVWGSIKGLT EGLHGFHVHE FGDNTAGCTS
61AGPHFNPLSR KHGGPKDEER HVGDLGNVTA DKDGVADVSI EDSVISLSGD HCIIGRTLVV
121HEKADDLGKG GNEESTKTGN AGSRLACGVI GIAQ

Sites are UniProt's curated features where the seed is a UniProt accession; the substituted positions are measured from this family's own alignment rather than annotated, and only the fifteen most substituted are marked: every position carrying a minority substitution would be most of the protein, because the family holds orthologues. A residue can carry more than one and is drawn with the first that applies, in the order of the key above.

Primary citations

One record per paper, not per entry.

YearCitation
2026 The Mycobacterium abscessus cytochrome bcc:aa 3 oxidase structure paves the way for an agent targeting subunit QcrB. Nat Commun doi:10.1038/s41467-026-70805-5
2026 Structural analysis of Cu/Zn-superoxide dismutase linked to neurodegenerative disease by antibody-guided cryo-EM. Protein Sci. doi:10.1002/pro.70615
2025 Cu/Zn-superoxide dismutase naturally fused with a beta-propeller lactonase in Deinococcus radiodurans. J.Biol.Chem. doi:10.1016/j.jbc.2025.110499
2025 Structural mechanisms and insights on multiple nanobodies binding diverse SOD1 epitopes. Commun Biol doi:10.1038/s42003-025-09293-0
2025 Temperature-Dependent Structural Dynamics of SOD1 Revealed by Serial Synchrotron Crystallography Abant Med J doi:10.47493/abantmedj.1817591
2025 Structural Insights into the Dynamics of Water in SOD1 Catalysis and Drug Interactions. Int J Mol Sci doi:10.3390/ijms26094228
2025 Distinct amyloid fibril structures formed by ALS-causing SOD1 mutants G93A and D101N. Embo Rep. doi:10.1038/s44319-025-00557-8
2025 Structural insights into the role of reduced cysteine residues in SOD1 amyloid filament formation. Proc.Natl.Acad.Sci.USA doi:10.1073/pnas.2408582122
2024 Ebselen analogues delay disease onset and its course in fALS by on-target SOD-1 engagement. Sci Rep doi:10.1038/s41598-024-62903-5
2024 Evaluating protein cross-linking as a therapeutic strategy to stabilize SOD1 variants in a mouse model of familial ALS. Plos Biol. doi:10.1371/journal.pbio.3002462
2024 Structural insights into the modulation Of SOD1 aggregation By a fungal metabolite Phialomustin-B: Therapeutic potential in ALS. Plos One doi:10.1371/journal.pone.0298196
2024 Disulfide-mediated oligomerization of mutant Cu/Zn-superoxide dismutase associated with canine degenerative myelopathy. Protein Sci. doi:10.1002/pro.5210
2024 Amyloid fibril structures and ferroptosis activation induced by ALS-causing SOD1 mutations. Sci Adv
2023 Intrinsic structural vulnerability in the hydrophobic core induces species-specific aggregation of canine SOD1 with degenerative myelopathy-linked E40K mutation. J.Biol.Chem. doi:10.1016/j.jbc.2023.104798
2023 Characterization of a novel cysteine-less Cu/Zn-superoxide dismutase in Paenibacillus lautus missing a conserved disulfide bond. J.Biol.Chem. doi:10.1016/j.jbc.2023.105040
2023 Hydrogen sulfide functions as a micro-modulator bound at the copper active site of Cu/Zn-SOD to regulate the catalytic activity of the enzyme. Cell Rep doi:10.1016/j.celrep.2023.112750
2023 Direct relationship between dimeric form and activity in the acidic copper-zinc superoxide dismutase from lemon. Acta Crystallogr.,Sect.F doi:10.1107/S2053230X23010646
2023 Structure-based discovery of an antipsychotic drug, paliperidone, as a modulator of human superoxide dismutase 1: a potential therapeutic target in amyotrophic lateral sclerosis. Acta Crystallogr D Struct Biol doi:10.1107/S2059798323003649
2023 Structure of a superoxide dismutase from a tardigrade: Ramazzottius varieornatus strain YOKOZUNA-1. Acta Crystallogr.,Sect.F doi:10.1107/S2053230X2300523X
2022 Structural analysis of the overoxidized Cu/Zn-superoxide dismutase in ROS-induced ALS filament formation. Commun Biol doi:10.1038/s42003-022-04017-0
2022 Cryo-EM structure of an amyloid fibril formed by full-length human SOD1 reveals its conformational conversion. Nat Commun doi:10.1038/s41467-022-31240-4
2021 Bacterial Evolutionary Precursors of Eukaryotic Copper-Zinc Superoxide Dismutases. Mol.Biol.Evol. doi:10.1093/molbev/msab157
2021 Crystal Structure of a Cu,Zn Superoxide Dismutase From the Thermophilic Fungus Chaetomium thermophilum. Protein Pept.Lett. doi:10.2174/0929866528666210316104919
2021 Transient Diffusive Interactions with a Protein Crowder Affect Aggregation Processes of Superoxide Dismutase 1 beta-Barrel. J.Phys.Chem.B doi:10.1021/acs.jpcb.0c11162
2020 Novel Selenium-based compounds with therapeutic potential for SOD1-linked amyotrophic lateral sclerosis. Ebiomedicine doi:10.1016/j.ebiom.2020.102980
2020 Ebselen as template for stabilization of A4V mutant dimer for motor neuron disease therapy. Commun Biol doi:10.1038/s42003-020-0826-3
2019 Molecular recognition and maturation of SOD1 by its evolutionarily destabilised cognate chaperone hCCS. Plos Biol. doi:10.1371/journal.pbio.3000141
2019 Rational discovery of a SOD1 tryptophan oxidation inhibitor with therapeutic potential for amyotrophic lateral sclerosis. J.Biomol.Struct.Dyn. doi:10.1080/07391102.2018.1531787
2018 The cysteine-reactive small molecule ebselen facilitates effective SOD1 maturation. Nat Commun doi:10.1038/s41467-018-04114-x
2018 The Cost of Long Catalytic Loops in Folding and Stability of the ALS-Associated Protein SOD1. J.Am.Chem.Soc. doi:10.1021/jacs.8b08141
2018 Assessment of ligand binding at a site relevant to SOD1 oxidation and aggregation FEBS Lett. doi:10.1002/1873-3468.13055
2018 Interaction of Half Oxa-/Halfcis-Platin Complex with Human Superoxide Dismutase and Induced Reduction of Neurotoxicity. ACS Med Chem Lett doi:10.1021/acsmedchemlett.8b00199
2017 Copper-zinc superoxide dismutase is activated through a sulfenic acid intermediate at a copper ion entry site. J. Biol. Chem. doi:10.1074/jbc.M117.775981
2016 Tricking a Protein To Swap Strands. J. Am. Chem. Soc. doi:10.1021/jacs.6b05151
2016 A Phosphomimetic Mutation Stabilizes SOD1 and Rescues Cell Viability in the Context of an ALS-Associated Mutation. Structure doi:10.1016/j.str.2016.08.011
2016 SALS-linked WT-SOD1 adopts a highly similar helical conformation as FALS-causing L126Z-SOD1 in a membrane environment Biochim.Biophys.Acta doi:10.1016/j.bbamem.2016.06.027
2015 Insights into the role of the unusual disulfide bond in copper-zinc superoxide dismutase. J.Biol.Chem. doi:10.1074/jbc.M114.588798
2015 The megavirus chilensis cu,zn-superoxide dismutase: the first viral structure of a typical cellular copper chaperone-independent hyperstable dimeric enzyme. J.Virol. doi:10.1128/JVI.02588-14
2015 Thermodynamics of protein destabilization in live cells. Proc. Natl. Acad. Sci. U.S.A. doi:10.1073/pnas.1511308112
2015 Mechanism for transforming cytosolic SOD1 into integral membrane proteins of organelles by ALS-causing mutations Biochim.Biophys.Acta doi:10.1016/j.bbamem.2014.10.002