| Feature | Description | Evidence/Citation |
|---|---|---|
| Protein structure | Human SOD1 is a mature **~32 kDa homodimer** composed of two **153-aa monomers (~16 kDa each)**. Each monomer forms an **eight-stranded β-barrel** with prominent **metal-binding**, **disulfide**, **electrostatic**, and **Greek key** loop elements. The electrostatic loop helps steer anionic substrate into the active site, and the dimer interface buries substantial hydrophobic surface, contributing to exceptional stability of holo-SOD1. | (pqac-00000007, pqac-00000009) |
| Metal cofactors | SOD1 is a **Cu/Zn metalloenzyme**. **Cu** at the catalytic site is coordinated by **His46, His48, His63, and His120**, with a water ligand completing a square-pyramidal geometry; these residues support Cu(I)/Cu(II) redox cycling. **Zn** is coordinated in a distorted tetrahedral site by **His63, His71, His80, and Asp83**, stabilizing the active-site architecture and loop conformations required for function. | (pqac-00000007, pqac-00000009) |
| Primary enzymatic reaction | The canonical reaction is **superoxide dismutation**: **2 O2•− + 2 H+ → H2O2 + O2**. Thus, the **substrate specificity** is for the **superoxide anion radical (O2•−)**, and the products are **hydrogen peroxide** and **molecular oxygen**. This reaction is a first-line antioxidant defense against intracellular superoxide. | (pqac-00000006, pqac-00000008, pqac-00000009) |
| Catalytic mechanism | Catalysis depends on **copper redox cycling** between **Cu(I)** and **Cu(II)** at the active site. One superoxide is oxidized to O2 while reducing Cu(II) to Cu(I); a second superoxide is then reduced to H2O2 as Cu(I) is reoxidized to Cu(II). Catalysis occurs at or near the **diffusion limit**, aided by an **electrostatic guidance system** in the electrostatic loop; **Arg143** is specifically important for substrate attraction and nonsubstrate exclusion. | (pqac-00000001, pqac-00000009) |
| Subcellular localization | SOD1 is found primarily in the **cytosol**, but also in the **mitochondrial intermembrane space** and **nucleus** under normal and pathological conditions. Reviews also note **extracellular/secreted SOD1** via unconventional secretion and circulation in blood-associated compartments, extending function beyond the strictly intracellular space. | (pqac-00000006, pqac-00000008, pqac-00000012) |
| Post-translational maturation requirements | Functional maturation requires **(1) Zn binding, (2) Cu insertion, (3) oxidation of the intramonomeric disulfide bond Cys57–Cys146, and (4) homodimerization**. The mature enzyme is highly stable, whereas **apo-SOD1** is markedly less stable. Copper incorporation is mediated by the **copper chaperone for SOD1 (CCS)**, and proper metallation/disulfide formation are essential for catalytic activity and structural integrity. | (pqac-00000007, pqac-00000009) |
| Novel regulatory functions | Beyond detoxifying superoxide, SOD1-derived **H2O2** can function in **redox signaling**. Experimental work showed SOD1 **interacts with GAPDH**, promotes **GAPDH thiol oxidation**, lowers GAPDH activity, and thereby helps reroute carbon flux from **glycolysis** to the **oxidative pentose phosphate pathway**, increasing **NADPH** production and oxidative-stress resistance. This places SOD1 as a regulator of metabolic adaptation, not just a scavenger enzyme. | (pqac-00000003, pqac-00000010, pqac-00000012) |
| Hydrogen sulfide oxidase activity | Recent literature and UniProt-linked annotation indicate a **non-canonical H2S-related activity** for Cu/Zn-SOD1, including description as **“hydrogen sulfide oxidase”** and evidence that **H2S binds at the copper active site** to modulate catalytic behavior. Available accessible review sources describe this as a newly emerging role of SOD1 beyond classical superoxide dismutation; however, mechanistic depth is more limited in the presently available contexts than for canonical activity. | (pqac-00000000, pqac-00000009) |


*Table: This table compiles the main structural, catalytic, localization, maturation, and emerging regulatory properties of human SOD1. It is useful as a compact evidence-based reference for functional annotation of UniProt P00441.*