Iduronate 2-sulfatase (I2S) !

Iduronate 2-sulfatase strips the sulfate off iduronic acid in dermatan and heparan sulfate. Its loss causes Hunter syndrome (MPS II).

Updated 2026-11-01

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Key facts

It removes the 2-sulfate from α-L-iduronic acid at the end of dermatan sulfate and heparan sulfate; only then can α-L-iduronidase cut the sugar off.
IDS gene on Xq28: MPS II (Hunter) is the only X-linked mucopolysaccharidosis, so it affects almost only boys.
Like every sulfatase it needs a formylglycine in its active site, made from a cysteine by the formylglycine-generating enzyme (SUMF1); without SUMF1 all sulfatases fail (multiple sulfatase deficiency).
One Ca²⁺ ion sits next to the formylglycine; the 3D model centres the active site on that calcium (PDB 5FQL, human enzyme).

Works at the acid pH of the lysosome.
Made as a larger precursor and cut by proteolysis into its mature, active chains.
Reaches the lysosome tagged with mannose 6-phosphate; secreted enzyme can be taken up by neighbouring cells (cross-correction).

No inhibitor is used in medicine; the clinically relevant molecule is the recombinant enzyme given as replacement therapy.

Hunter syndrome: coarse features, hepatosplenomegaly, stiff joints, valve disease and airway obstruction, with clear corneas (unlike Hurler).
Diagnosis: raised urine dermatan and heparan sulfate, low I2S activity with another sulfatase normal (to exclude multiple sulfatase deficiency), and IDS gene testing.
Intravenous enzyme replacement improves organs, breathing and movement but does not cross the blood–brain barrier.

Think of the answer, then tap the question to see it.

Which enzyme acts right after iduronate 2-sulfatase on dermatan sulfate?

α-L-Iduronidase, which removes the now unsulfated iduronic acid; it is the enzyme missing in Hurler syndrome.

Why does Hunter syndrome affect almost only males?

The IDS gene is on the X chromosome, so a boy with one altered copy has no working enzyme, while carrier girls keep a normal copy.

Which modified residue must every human sulfatase carry in its active site?

A formylglycine made from a cysteine by SUMF1; if SUMF1 fails, all sulfatases fail together (multiple sulfatase deficiency).

How do Hunter and Hurler syndromes differ at the eye?

The corneas stay clear in Hunter syndrome and become cloudy in Hurler syndrome.

Educational information, not medical advice. For any symptom, see a health professional.

Sources: IDS: Iduronate 2-sulfatase (human) (UniProt, 2026); IDS gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); RCSB PDB - 5FQL: Insights into Hunter syndrome from the structure of iduronate-2- sulfatase (RCSB Protein Data Bank, 2026); MPS II - Hunter syndrome (HS-GAG degradation) (Reactome, 2026); Textbook of Biochemistry for Medical Students, 6th ed. (Jaypee Brothers Medical Publishers (Vasudevan DM, Sreekumari S, Vaidyanathan K), 2011).

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Representative model, for educational purposes only.