- Aspartate protease
Pfam_box
Symbol = Asp
Name = Eukaryotic aspartyl protease
width = 180
caption =
Pfam= PF00026
InterPro= IPR001461
SMART=
PROSITE = PDOC00128
SCOP = 1mpp
TCDB =
OPM family= 108
OPM protein= 1lyb
PDB=PDB3|1j71A:73-383 PDB3|1eagA:69-386 PDB3|1zap :69-386PDB3|1ypsA:157-477 PDB3|2rmpA:88-423 PDB3|2asi :88-423PDB3|1mpp :85-420 PDB3|1bbsA:85-405 PDB3|1bimB:85-405PDB3|1bilA:85-405 PDB3|1hrnB:85-405 PDB3|1rne :85-405PDB3|1pr7B:85-405 PDB3|1pr8A:85-405 PDB3|2ren :85-405PDB3|1uhqA:85-405 PDB3|1g0vA:90-404 PDB3|1fmxB:90-404PDB3|1dp5A:90-404 PDB3|1fq5A:90-404 PDB3|1dpjA:90-404PDB3|1fq4A:90-404 PDB3|1fmuA:90-404 PDB3|2jxrA:90-404PDB3|1fq7A:90-404 PDB3|1fq6A:90-404 PDB3|1fq8A:90-404PDB3|1lywC:78-161 PDB3|1lybA:78-161 PDB3|1lyaC:78-161PDB3|1b5fB:418-503 PDB3|1qrpE:75-387 PDB3|1psn :75-387PDB3|1psoE:75-387 PDB3|1flhA:75-387 PDB3|3pep :72-384PDB3|1f34A:72-384 PDB3|5pep :72-384 PDB3|1psaB:72-384PDB3|4pep :72-384 PDB3|3psgA:72-384 PDB3|1am5 :13-323PDB3|1cziE:73-380 PDB3|1cms :73-380 PDB3|3cms :73-380PDB3|4cms :73-380 PDB3|1lcgA:77-399 PDB3|1htrB:72-387PDB3|1avfA:72-387 PDB3|1ls5A:136-446 PDB3|1miqB:138-448PDB3|1qs8B:138-448 PDB3|1m43B:139-449 PDB3|1smeA:139-449PDB3|1pfzA:139-449 PDB3|1xe6B:139-449 PDB3|2bjuA:139-449PDB3|1lf3A:139-449 PDB3|1xdhB:139-449 PDB3|1leeA:139-449PDB3|1xe5A:139-449 PDB3|2bl3A:139-449 PDB3|1j8jA:139-449PDB3|1me6B:139-449 PDB3|1lf2A:139-449 PDB3|1lf4A:139-449PDB3|1lduA:138-448 PDB3|1lcrA:138-448 PDB3|1qyjA:140-448PDB3|1kbxA:138-447 PDB3|1wkrA:13-332 PDB3|2er0E:105-419PDB3|4er1E:105-419 PDB3|1epoE:105-419 PDB3|1oexA:105-419PDB3|1entE:105-419 PDB3|4er4E:105-419 PDB3|5er1E:105-419PDB3|1gvtA:105-419 PDB3|2er7E:105-419 PDB3|3er5E:105-419PDB3|5er2E:105-419 PDB3|1oewA:105-419 PDB3|2er9E:105-419PDB3|4er2E:105-419 PDB3|1e81E:105-419 PDB3|1gvvA:105-419PDB3|1epnE:105-419 PDB3|3er3E:105-419 PDB3|4ape :105-419PDB3|1epqE:105-419 PDB3|1gvxA:105-419 PDB3|1eppE:105-419PDB3|1eedP:105-419 PDB3|1e5oE:105-419 PDB3|1e82E:105-419PDB3|1od1A:105-419 PDB3|1epmE:105-419 PDB3|1eprE:105-419PDB3|2er6E:105-419 PDB3|1e80E:105-419 PDB3|1eplE:105-419PDB3|1gvuA:105-419 PDB3|1er8E:105-419 PDB3|1gvwA:105-419PDB3|1ibqA:84-393 PDB3|1apvE:16-322 PDB3|2wec :16-322PDB3|2wed :16-322 PDB3|1ppmE:16-322 PDB3|1bxoA:16-322PDB3|1aptE:16-322 PDB3|1apwE:16-322 PDB3|1bxqA:16-322PDB3|1pplE:16-322 PDB3|1apuE:16-322 PDB3|2web :16-322PDB3|1ppkE:16-322 PDB3|2wea :16-322 PDB3|3app :16-322PDB3|6aprE:84-391 PDB3|5aprE:84-391 PDB3|4aprE:84-391PDB3|2apr :84-391 PDB3|3aprE:84-391 PDB3|1uh8A:83-340PDB3|1uh7A:83-340 PDB3|1uh9A:83-340 PDB3|1sgzD:74-418PDB3|2fdpC:74-418 PDB3|1xn2B:74-418 PDB3|2b8vA:74-418PDB3|1w51A:74-418 PDB3|1tqfA:74-418 PDB3|1xs7D:74-418PDB3|1xn3B:74-418 PDB3|1m4hA:74-418 PDB3|1ym2A:74-418PDB3|1w50A:74-418 PDB3|2b8lA:74-418 PDB3|1ym4C:74-418PDB3|1fknB:74-418 PDB3|1yg9A:38-348Aspartic proteases are a family of eukaryotic
protease enzymes that utilize anaspartate residue for catalysis of their peptide substrates. In general, they have two highly-conservedaspartate s in theactive site and are optimally active at acidicpH . Nearly all known aspartyl proteases are inhibited bypepstatin .Eukaryotic aspartic proteases include
pepsin s,cathepsin s, andrenin s. They have a two-domain structure, probably arising from ancestral duplication. Retroviral andretrotransposon proteases (Pfam|PF00077) are much smaller and appear tobe homologous to a single domain of the eukaryotic aspartyl proteases.Examples
*
HIV-1 protease - a major drug-target for treatment ofHIV
*Chymosin (or "rennin", with two "n"s)
*Renin (with one "n")
*Cathepsin D
*Pepsin
*Plasmepsin Mechanism
While a number of different mechanisms for aspartyl proteases have been proposed, the most widely accepted is a general acid-base mechanism involving coordination of a water molecule between the two highly-conserved
aspartate residues.cite journal |author=Suguna K, Padlan EA, Smith CW, Carlson WD, Davies DR |title=Binding of a reduced peptide inhibitor to the aspartic proteinase from Rhizopus chinensis: implications for a mechanism of action |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=84 |issue=20 |pages=7009–13 |year=1987 |pmid=3313384 |doi=] cite journal |author=Brik A, Wong CH |title=HIV-1 protease: mechanism and drug discovery |journal=Org. Biomol. Chem. |volume=1 |issue=1 |pages=5–14 |year=2003 |pmid=12929379 |doi=] One aspartate activates the water by abstracting a proton, enabling the water to attack thecarbonyl carbon of the substrate scissile bond, generating a tetrahedral oxyanion intermediate. Rearrangement of this intermediate leads to protonation of the scissile amide.ubfamilies
*
Peptidase A1, beta-site APP cleaving enzyme, BACE InterPro|IPR009119Human proteins containing this domain
BACE ;BACE1 ;BACE2 ;CTSD ;CTSE ;NAPSA ;PGA5 ;PGC ;REN ;External links
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References
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