Idursulfase

  • OMIM: 309900
  • UniProt: P22304
  • MGI: 96 417
  • CAS Number: 50936-59-9

Iduronate -2 -sulfatase (IDS, formerly Chondroitinsulfatase ) is an enzyme found in all living things, specifically in eukaryotes has the task of collaborating in the lysosomes in the digestion of certain substances within the cell. It cleaves heparan sulfate and dermatan sulfate from the main component of the fibers and the cartilage tissue in the body. It is thus indispensable part of the pathway, which degrades these substances in the body. Missing IDS in the body, for example by mutation of IDS gene, resulting in humans Hunter syndrome. Idursulfase (trade name: Elaprase ®, manufactured by Shire ) is a drug with this enzyme, which is used in the treatment of Hunter syndrome.

  • 4.1 Therapeutic indications (indications )

Biosynthesis

The gene originates from the IDS, located on the X chromosome and extends over nine exons and 26,500 base pairs. The transcript is 5756 bases long and translates into a 550 amino acid -containing precursor protein having 422 amino acids long and 42 kDa and a 95 amino acids long and 12 kDa obtained by the post-translational modification heavy protein chains which combine both the final enzyme. From the precursor, there is a short isoform in which 157 amino acids are lacking.

Biological Function

IDS is mainly formed in the liver, kidney, lung and placenta. There in the lysosomes of cells amplified endogenous and exogenous macromolecules ( glycosaminoglycans ) are terminated. The task of IDS is the hydrolytic cleavage of organic sulfates such as heparin sulfate, dermatan sulfate and heparin. For this function, the enzyme per unit requires a calcium ion as a cofactor.

Catalyzed reaction

In the degradation of dermatan

IdoA ( 2S) β1 - 3GalNAc ( 4S) β1 - 3GalNAc 4GlcAβ1 - (4S ) H2O: IdoAβ1 - 3GalNAc ( 4S) β1 - 3GalNAc 4GlcAβ1 - (4S ) sulfate

The degradation of heparan sulfate

IdoA ( 2S) β1 - 4GlcN ( 2S) α1 - 4GlcA ( 2S) β1 - 4GlcNAc ( 6S) α1 - 4GlcA H2O: IdoAβ1 - 4GlcN ( 2S) α1 - 4GlcA ( 2S) β1 - 4GlcNAc ( 6S) α1 - 4GlcA sulfate

Pharmacology

Idursulfase is the recombinant form of human lysosomal enzyme iduronate -2-sulfatase, and is produced by a human cell line.

Areas of application (indications )

Long -term treatment of patients with Hunter Syndrome ( mucopolysaccharidosis II, MPS II).

Treatment costs

The cost of treatment per patient per year are between € 390,000 (5- year-old child, 25 kg) and € 1.1 million ( Adult, 70 kg).

Protein isoform Human Genome Organisation Mouse Genome Informatics CAS registry number Anatomical Therapeutic Chemical Classification System DrugBank Hydrolysis Organism Entrez Ensembl National Center for Biotechnology Information Active ingredient
301771
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