Iduronate 2 sulfatase

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Iduronate-2-sulfatase
Properties of human protein
Mass / length primary structure 517 amino acids
Secondary to quaternary structure Heterodimer
Cofactor Ca 2+
Precursor (343/550 aa)
Isoforms short long
Identifier
Gene names IDS  ; MPS2; SIDS
External IDs
Drug information
ATC code A16 AB09
DrugBank DB01271
Enzyme classification
EC, category 3.1.6.13 ,  sulfatase
Response type hydrolysis
Substrate L-iduronate-2-sulfate
Occurrence
Homology family Iduronate-2-sulfatase
Parent taxon Creature
Exceptions plants
Orthologue
human mouse
Entrez 3423 15931
Ensemble ENSG00000010404 ENSMUSG00000035847
UniProt P22304 Q8CJ15
Refseq (mRNA) NM_000202 NM_001038990
Refseq (protein) NP_000193 NP_001034079
Gene locus Chr X: 148.37 - 148.39 Mb Chr X: 66.6 - 66.63 Mb
PubMed search 3423 15931

Iduronate-2-sulfatase ( IDS , formerly Chondroitinsulfatase ) is in all living organisms occurring enzyme , specifically in eukaryotes has the task in the lysosomes in the digestion of certain substances within the cell participate. It breaks down sulfate from dermatan sulfate and heparan sulfate , which are the main constituents of fibers and cartilage tissue in the body. It is therefore an indispensable part of the reaction pathway that breaks down these substances in the body. If IDS is missing in the body, for example due to a mutation of the IDS gene , Hunter syndrome results in humans . Idursulfase (trade name: Elaprase ® , manufacturer: Shire plc ) is a drug containing this enzyme and is used in the treatment of Hunter syndrome.

biosynthesis

The gene that creates IDS is located on the X chromosome and spans nine exons and 26,500 base pairs. The transcript is 5756 bases long and translated into a 550 amino acid precursor protein which, after post-translational modification, results in a 422 amino acid long and 42  kDa protein chain and a 95 amino acid long and 12 kDa protein chain, both of which combine to form the final enzyme. There is a short isoform of the precursor that is missing 157 amino acids.

Biological function

IDS is mainly formed in the liver , kidneys , lungs, and placenta . There, the body's own and foreign macromolecules ( glycosaminoglycans ) are increasingly broken down in the lysosomes of the cells . The task of IDS is the hydrolytic cleavage of organic sulfates such as heparin sulfate , dermatan sulfate and heparin . For this function the enzyme needs one calcium ion per unit as a cofactor.

Catalyzed reaction

When breaking down dermatan sulfate

IdoA (2S) β1-3GalNAc (4S) β1-4GlcAβ1-3GalNAc (4S) + H 2 O: IdoAβ1-3GalNAc (4S) β1-4GlcAβ1-3GalNAc (4S) + sulfate

When breaking down heparan sulfate

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

pharmacology

Idursulfase is the recombinantly produced form of the human lysosomal enzyme iduronate-2-sulfatase and is produced using a human cell line .

Application areas (indications)

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

Treatment costs

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

Web links

Wikibooks: Biochemistry and Pathobiochemistry: Degradation of Glycosaminoglycans  - Learning and Teaching Materials

Individual evidence

  1. ↑ Red List online, as of October 2009.
  2. ↑ UniProt P22304
  3. ↑ Ensembl entries .
  4. ↑ D. Paffrath: Drug Ordinance Report 2008. Verlag Springer, 2008, ISBN 3-540-69218-5 , p. 75. Restricted preview in the Google book search