Iduronate 2-sulfatase (IDS), also referred to as Alpha-L-iduronate sulfate sulfatase or Idursulfase, is a lysosomal enzyme involved in the degradation pathway of dermatan sulfate and heparan sulfate.[1]
Function
Iduronate 2-sulfatase is located in the lysosome.[1] It is involved in the lysosomal degradation pathway of dermatan sulfate and heparan sulfate.[1] IDS hydrolyzes the 2-sulfate groups of the L-iduronate 2-sulfate units of dermatan sulfate, heparan sulfate and heparin.[1] Dermatan sulfate and heparan sulfate are complex glycosaminoglycans, which are essentially large sugar molecules.[2] They play important roles in cell adhesion, growth, proliferation and repair, and their degradation and recycling in the lysosome are essential for cellular maintenance.[2] IDS is expressed in the tissues of the liver, kidney, lung, and placenta.[1]
Disease
Mutations in Iduronate 2-sulfatase on the Xq28 chromosome can lead to Mucopolysaccharidosis 2 (MPS2), more commonly known as Hunter syndrome.[1] MPS2 is an X-linked lysosomal storage disease.[1] Due to the loss of IDS activity, the disease is characterized by the intracellular accumulation of the glycosaminoglycans heparan sulfate and dermatan sulfate, which are then excreted in urine.[1] Scientists have identified over 500 mutations on the Xq28 chromosome that include rearrangements, insertions/deletions, splicing defects and nonsense point mutations.[2] It is rare to find adults with severe Hunter syndrome as the average life expectancy for those with MPS2 is 15 years of age.[1] Most children diagnosed with MPS2 have somatic abnormalities including skeletal deformities, hepatosplenomegaly, and progressive cardiopulmonary deterioration.[1] Neurological damage is also prevalent beginning with what seems to be a developmental delay and hyperactivity, but progresses to mental retardation and dementia.[1] Death from MPS2 is typically due to obstructive airway disease or cardiac failure.[1] A treatment for patients with mild Hunter syndrome is enzyme replacement therapy, which involves the recombinant human IDS.[2]
Structural highlights
