| Eukaryotic aspartyl protease | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 Structure of the dimeric aspartic protease HIV protease in white and grey, with peptide substrate in black and active site aspartate side chains in red. (PDB: 1KJF) | |||||||||
| Identifiers | |||||||||
| Symbol | Asp | ||||||||
| Pfam | PF00026 | ||||||||
| InterPro | IPR001461 | ||||||||
| PROSITE | PDOC00128 | ||||||||
| SCOP2 | 1mpp / SCOPe / SUPFAM | ||||||||
| OPM superfamily | 100 | ||||||||
| OPM protein | 1lyb | ||||||||
| Membranome | 315 | ||||||||
| |||||||||
Aspartic proteases (also "aspartyl proteases", "aspartic endopeptidases") are a catalytic type of protease enzymes that use an activated water molecule bound to one or more aspartate residues for catalysis of their peptide substrates. In general, they have two highly conserved aspartates in the active site and are optimally active at acidic pH. Nearly all known aspartyl proteases are inhibited by pepstatin.[1]
Aspartic endopeptidases EC 3.4.23. of vertebrate, fungal and retroviral origin have been characterised.[2] More recently, aspartic endopeptidases associated with the processing of bacterial type 4 prepilin[3] and archaean preflagellin have been described.[4][5]
Eukaryotic aspartic proteases include pepsins, cathepsins, and renins. They have a two-domain structure, arising from ancestral duplication. Retroviral and retrotransposon proteases (retroviral aspartyl proteases) are much smaller and appear to be homologous to a single domain of the eukaryotic aspartyl proteases. Each domain contributes a catalytic Asp residue, with an extended active site cleft localized between the two lobes of the molecule. One lobe has probably evolved from the other through a gene duplication event in the distant past. In modern-day enzymes, although the three-dimensional structures are very similar, the amino acid sequences are more divergent, except for the catalytic site motif, which is very conserved. The presence and position of disulfide bridges are other conserved features of aspartic peptidases.
- ^ Fusek M, Mares M, Vetvicka V (2013-01-01). "Chapter 8 - Cathepsin D". In Rawlings ND, Salvesen G (eds.). Handbook of Proteolytic Enzymes (Third ed.). Academic Press. pp. 54–63. doi:10.1016/b978-0-12-382219-2.00008-9. ISBN 978-0-12-382219-2.
- ^ Szecsi PB (1992). "The aspartic proteases". Scandinavian Journal of Clinical and Laboratory Investigation. Supplementum. 210: 5–22. doi:10.3109/00365519209104650. PMID 1455179.
- ^ LaPointe CF, Taylor RK (January 2000). "The type 4 prepilin peptidases comprise a novel family of aspartic acid proteases". The Journal of Biological Chemistry. 275 (2): 1502–10. doi:10.1074/jbc.275.2.1502. PMID 10625704.
- ^ Ng SY, Chaban B, Jarrell KF (2006). "Archaeal flagella, bacterial flagella and type IV pili: a comparison of genes and posttranslational modifications". Journal of Molecular Microbiology and Biotechnology. 11 (3–5): 167–91. doi:10.1159/000094053. PMID 16983194. S2CID 30386932.
- ^ Bardy SL, Jarrell KF (November 2003). "Cleavage of preflagellins by an aspartic acid signal peptidase is essential for flagellation in the archaeon Methanococcus voltae". Molecular Microbiology. 50 (4): 1339–47. doi:10.1046/j.1365-2958.2003.03758.x. PMID 14622420. S2CID 11913649.