Cathepsin A

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Template:Short description Template:Cs1 config Template:Infobox gene Cathepsin A is an enzyme that is classified both as a cathepsin and a carboxypeptidase. In humans, it is encoded by the CTSA gene.[1] The enzyme is also known as Human Protective Protein.[2] It is a lysosomal serine carboxypeptidase. The enzyme is a zymogen and must be processed to produce a 32 kDa and 20 kDa large and small subunit, respectively, to become catalytically active. Cathespin L can activate Cathepsin A in vitro.[3][4]

Structure

Cathepsin A contains a large and small subunit. The active site contains unusual pairs of carboxylic acids hydrogen bonded to one another, sometimes referred to as "Rebek pairs".[5]

File:CatA.jpg
Active site of Cathepsin A. In green is the Rebek pair. The two glutamate side chains are directed towards one another. To prevent an unfavorable charge-charge interaction the pKa of one glutamate side chain is raised to ~13.

The pairing of these carboxylic acids raises the pKa of one glutamate to ~13 while the other has a predicted pKa of ~6.[6]

Function

This gene encodes a glycoprotein that associates with lysosomal enzymes beta-galactosidase and neuraminidase to form a complex of high-molecular-weight multimers. The formation of this complex provides a protective role for stability and activity. It is protective for β-galactosidase and neuraminidase.[7]

Substrates

CTSA is part of the Renin Angiotensin System (RAS). Substrates of the enzyme that have been identified in vitro include endothelin I, angiotensin I, bradykinin, Substance P, and oxytocin.

File:CatASubstrate.jpg
Peptide substrates of Cathepsin A. CTSA is part of the Renin-Angiotensin System (RAS)

Inhibition

Cathepsin A is one of 14 human enzymes commonly inhibited by organophosphate pesticides and phosphonate nerve agents. Cathepsin A can be inhibited by sarin, soman, cyclosarin, VX, and VR.[8] After inhibition, it undergoes aging. The enzyme can be found in urine and blood.

Clinical significance

Deficiencies in this gene are linked to multiple forms of galactosialidosis and CARASAL.[1][9]

Interactions

Cathepsin A has been shown to interact with NEU1 and GLB1.[10]

References

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Further reading

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External links

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