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InterPro: IPR009007 Peptidase aspartic, catalytic
Protein matches
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UniProtKB Matches: 93516 proteins |
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Accession
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IPR009007 Peptidase_aspartic_catalytic |
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Type
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Domain |
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Signatures
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InterPro Relationships
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Children
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IPR000588 Peptidase A3A, cauliflower mosaic virus, catalytic
IPR001995 Peptidase A2A, retrovirus, catalytic
IPR019103 Peptidase aspartic, eukaryotic predicted
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Found in
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IPR001461 Peptidase A1
IPR009119 Peptidase A1, beta-site APP cleaving enzyme, BACE
IPR009120 Peptidase A1, beta-site APP cleaving enzyme 1, BACE 1
IPR009121 Peptidase A1, beta-site APP cleaving enzyme 2, BACE 2
IPR011969 Conserved hypothetical protein CHP02281
IPR013242 Retroviral aspartyl protease
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Contains
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IPR001969 Peptidase aspartic, active site
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GO Term annotation
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Process
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GO:0006508 proteolysis
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Function
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GO:0004190 aspartic-type endopeptidase activity
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InterPro annotation
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 Entry Details in BioMart
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Abstract
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In the MEROPS database peptidases and peptidase homologues are grouped into clans and families. Clans are groups of families for which there is evidence of common ancestry based on a common structural fold:
- Each clan is identified with two letters, the first representing the catalytic type of the families included in the clan (with the letter 'P' being used for a clan containing families of more than one of the catalytic types serine, threonine and cysteine). Some families cannot yet be assigned to clans, and when a formal assignment is required, such a family is described as belonging to clan A-, C-, M-, S-, T- or U-, according to the catalytic type. Some clans are divided into subclans because there is evidence of a very ancient divergence within the clan, for example MA(E), the gluzincins, and MA(M), the metzincins.
- Peptidase families are grouped by their catalytic type, the first character representing the catalytic type: A, aspartic; C, cysteine; G, glutamic acid; M, metallo; S, serine; T, threonine; and U, unknown. The serine, threonine and cysteine peptidases utilise the amino acid as a nucleophile and form an acyl intermediate - these peptidases can also readily act as transferases. In the case of aspartic, glutamic and metallopeptidases, the nucleophile is an activated water molecule.
In many instances the structural protein fold that characterises the clan or family may have lost its catalytic activity, yet retain its function in protein recognition and binding.
Aspartic endopeptidases EC:3.4.23. of vertebrate, fungal and retroviral origin have been characterised [1]. More recently, aspartic endopeptidases associated with the processing of bacterial type 4 prepilin [2] and archaean preflagellin have been described [3, 4].
Structurally, aspartic endopeptidases are bilobal enzymes, each lobe contributing a catalytic Asp residue, with an extended active site cleft localised 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 disulphide bridges are other conserved features of aspartic peptidases.
All or most aspartate peptidases are endopeptidases. These enzymes have been assigned into clans (proteins which are evolutionary related), and further sub-divided into families, largely on the basis of their tertiary structure.
These aspartate proteases all contain a common closed beta barrel structure, which includes pepsin, cathepsin, chymosin, beta-secretase, plasmepsin, plant acid proteases and retroviral proteases [5, 6].
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Structural links
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Database links
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Additional Reading
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Altman MD, Nalivaika EA, Prabu-Jeyabalan M, Schiffer CA, Tidor B.
Computational design and experimental study of tighter binding peptides to an inactivated mutant of HIV-1 protease.
Proteins 70 2008 678-94
[PubMed: 17729291]
http://dx.doi.org/10.1002/prot.21514
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Coman RM, Robbins AH, Fernandez MA, Gilliland CT, Sochet AA, Goodenow MM, McKenna R, Dunn BM.
The contribution of naturally occurring polymorphisms in altering the biochemical and structural characteristics of HIV-1 subtype C protease.
Biochemistry 47 2008 731-43
[PubMed: 18092815]
http://dx.doi.org/10.1021/bi7018332
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Blum A, Bottcher J, Heine A, Klebe G, Diederich WE.
Structure-guided design of C2-symmetric HIV-1 protease inhibitors based on a pyrrolidine scaffold.
J. Med. Chem. 51 2008 2078-87
[PubMed: 18348517]
http://dx.doi.org/10.1021/jm701142s
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Iserloh U, Wu Y, Cumming JN, Pan J, Wang LY, Stamford AW, Kennedy ME, Kuvelkar R, Chen X, Parker EM, Strickland C, Voigt J.
Potent pyrrolidine- and piperidine-based BACE-1 inhibitors.
Bioorg. Med. Chem. Lett. 18 2008 414-7
[PubMed: 18023580]
http://dx.doi.org/10.1016/j.bmcl.2007.10.116
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Goodwin KD, Lewis MA, Long EC, Georgiadis MM.
Crystal structure of DNA-bound Co(III) bleomycin B2: Insights on intercalation and minor groove binding.
Proc. Natl. Acad. Sci. U.S.A. 105 2008 5052-6
[PubMed: 18362349]
http://dx.doi.org/10.1073/pnas.0708143105
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