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- * Eukaryotic and viral aspartyl proteases active site *
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-
- Aspartyl proteases (also known as acid proteases) (EC 3.4.23.-) are a widely
- distributed family of proteolytic enzymes [1,2,3] which is known to exist in
- vertebrates, fungi, plants, retroviruses and some plant viruses. The aspartate
- proteases of eukaryotes are monomeric enzymes which consist of two domains.
- Each domain contains an active site centered on a catalytic aspartyl residue.
- The two domains have most probably evolved from the duplication of an
- ancestral gene encoding a primordial domain. Currently known eukaryotic
- aspartyl proteases are:
-
- - Vertebrate gastric pepsins A and C (also known as gastricin).
- - Vertebrate chymosin (rennin), involved in digestion and which is used for
- cheese making.
- - Vertebrate lysosomal cathepsins D (EC 3.4.23.5) and E (EC 3.4.23.34).
- - Mammalian renin (EC 3.4.23.15) whose function is to generate angiotensin I
- from angiotensinogen in the plasma.
- - Fungal proteases such as aspergillopepsin A (EC 3.4.23.18), candidapepsin
- (EC 3.4.23.24), mucoropepsin (EC 3.4.23.23) (mucor rennin), endothiapepsin
- (EC 3.4.23.22), polyporopepsin (EC 3.4.23.29), and rhizopuspepsin
- (EC 3.4.23.21).
- - Yeast saccharopepsin (EC 3.4.23.25) (proteinase A) (gene PEP4). PEP4 is
- implicated in the posttranslational regulation of vacuolar hydrolases.
- - Yeast extracellular 'barrier' protein (gene BAR1). Probably a protease that
- cleaves alpha-factor and thus acts a an antagonist of the mating pheromone.
- - Fission yeast sxa1 which is involved in the degradation or processing of
- the mating pheromones.
-
- Most retroviruses and some plant viruses (such as badnaviruses) encode for an
- aspartyl protease which is an homodimer of a chain of about 95 to 125 amino
- acids. In most retroviruses the protease is encoded as a segment of a
- polyprotein which is cleaved during the maturation process of the virus. It
- is generally part of the pol polyprotein and, more rarely, of the gag
- polyprotein.
-
- The conservation of the sequence around the two aspartates of eukaryotic
- aspartyl proteases and around the single active site of the viral proteases
- allows to develop a single signature pattern for both group of proteases.
-
- -Consensus pattern: [LIVMFGAC]-[LIVMTADN]-[LIVFSA]-D-[ST]-G-[STAV]-[STAPDENQ]-
- x-[LIVMFSTNC]-x-[LIVMFGTA]
- [D is the active site residue]
- -Sequences known to belong to this class detected by the pattern: ALL.
- -Other sequence(s) detected in SWISS-PROT: 15.
- -Last update: June 1994 / Pattern and text revised.
-
- [ 1] Foltmann B.
- Essays Biochem. 17:52-84(1981).
- [ 2] Davies D.R.
- Annu. Rev. Biophys. Chem. 19:189-215(1990).
- [ 3] Rao J.K.M., Erickson J.W., Wlodawer A.
- Biochemistry 30:4663-4671(1991).
-