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InterPro: IPR001969 Peptidase aspartic, active site

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UniProtKB
Matches:
86921 proteins
AccessionHelp
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IPR001969 Peptidase_aspartic_AS
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Active_site
SignaturesHelp
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InterPro RelationshipsHelp
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Found in IPR001461 Peptidase A1
IPR001995 Peptidase A2A, retrovirus, catalytic
IPR009007 Peptidase aspartic, catalytic
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
IPR018061 Peptidase A2A, retrovirus RVP subgroup
GO Term annotationHelp
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Process GO:0006508 proteolysis
Function GO:0004190 aspartic-type endopeptidase activity
InterPro annotation
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AbstractHelp
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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.

This signature contains the active site residues which are conserved in eukaryotic and viral aspartyl proteases.
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PDB - click here
1a30 , 1a8g , 1a8k , 1a94 , 1a9m , 1aaq , 1aid , 1ajv , 1ajx , 1am5 , 1apt , 1apu , 1apv , 1apw , 1avf , 1axa , 1az5 , 1b11 , 1b5f , 1b6j , 1b6k , 1b6l , 1b6m , 1b6p , 1bai , 1bbs , 1bdl , 1bdq , 1bdr , 1bil , 1bim , 1bv7 , 1bv9 , 1bve , 1bvg , 1bwa , 1bwb , 1bxo , 1bxq , 1c6x , 1c6y , 1c6z , 1c70 , 1cms , 1cpi , 1czi , 1d4h , 1d4i , 1d4j , 1d4k , 1d4l , 1d4s , 1d4y , 1daz , 1dif , 1dmp , 1dp5 , 1dpj , 1dw6 , 1e5o , 1e80 , 1e81 , 1e82 , 1eag , 1ebk , 1ebw , 1eby , 1ebz , 1ec0 , 1ec1 , 1ec2 , 1ec3 , 1eed , 1ent , 1epl , 1epm , 1epn , 1epo , 1epp , 1epq , 1epr , 1er8 , 1f34 , 1f7a , 1fb7 , 1fej , 1ff0 , 1fff , 1ffi , 1fg6 , 1fg8 , 1fgc , 1fiv , 1fkn , 1flh , 1fmb , 1fmu , 1fmx , 1fq4 , 1fq5 , 1fq6 , 1fq7 , 1fq8 , 1fqx , 1g0v , 1g2k , 1g35 , 1g6l , 1gnm , 1gnn , 1gno , 1gvt , 1gvu , 1gvv , 1gvw , 1gvx , 1hbv , 1hef , 1heg , 1hhp , 1hih , 1hii , 1hiv , 1hos , 1hpo , 1hps , 1hpv , 1hpx , 1hrn , 1hsg , 1hsh , 1hsi , 1hte , 1htf , 1htg , 1htr , 1hvc , 1hvh , 1hvi , 1hvj , 1hvk , 1hvl , 1hvr , 1hvs , 1hwr , 1hxb , 1hxw , 1ibq , 1ida , 1idb , 1iiq , 1ivp , 1ivq , 1izh , 1izi , 1j71 , 1jld , 1k1t , 1k1u , 1k2b , 1k2c , 1k6c , 1k6p , 1k6t , 1k6v , 1kj4 , 1kj7 , 1kjf , 1kjg , 1kjh , 1kzk , 1lee , 1lf2 , 1lf3 , 1lf4 , 1ls5 , 1lv1 , 1lya , 1lyb , 1lyw , 1lzq , 1m0b , 1m43 , 1m4h , 1me6 , 1mer , 1mes , 1met , 1meu , 1miq , 1mpp , 1mrw , 1mrx , 1msm , 1msn , 1mt7 , 1mt8 , 1mt9 , 1mtb , 1mtr , 1mui , 1mvp , 1n49 , 1nh0 , 1npa , 1npv , 1npw , 1nso , 1od1 , 1odw , 1odx , 1ody , 1oew , 1oex , 1ohr , 1pfz , 1ppk , 1ppl , 1ppm , 1pro , 1psa , 1psn , 1pso , 1q9p , 1qbr , 1qbs , 1qbt , 1qbu , 1qdm , 1qrp , 1qs8 , 1rl8 , 1rne , 1rpi , 1rq9 , 1rv7 , 1sbg , 1sdt , 1sdu , 1sdv , 1sgu , 1sgz , 1sh9 , 1sip , 1siv , 1sme , 1smr , 1sp5 , 1t3r , 1t7i , 1t7j , 1t7k , 1tcw , 1tcx , 1tqf , 1tsq , 1tsu , 1tw7 , 1u8g , 1uh7 , 1uh8 , 1uh9 , 1upj , 1vij , 1vik , 1w50 , 1w51 , 1w5v , 1w5w , 1w5x , 1w5y , 1w6h , 1w6i , 1wbk , 1wbm , 1wkr , 1xdh , 1xe5 , 1xe6 , 1xl2 , 1xl5 , 1xn2 , 1xn3 , 1xs7 , 1ym2 , 1ym4 , 1yt9 , 1ytg , 1yth , 1yti , 1ytj , 1yx9 , 1z1h , 1z1r , 1z8c , 1zap , 1zbg , 1zj7 , 1zlf , 1zp8 , 1zpa , 1zpk , 1zsf , 1zsr , 1ztz , 2a1e , 2a4f , 2aid , 2anl , 2aoc , 2aod , 2aoe , 2aof , 2aog , 2aoh , 2aoi , 2aoj , 2apr , 2aqu , 2asi , 2avm , 2avo , 2avq , 2avs , 2avv , 2az8 , 2az9 , 2azb , 2azc , 2b60 , 2b7z , 2b8l , 2b8v , 2bb9 , 2bbb , 2bju , 2bpv , 2bpw , 2bpx , 2bpy , 2bpz , 2bqv , 2cej , 2cem , 2cen , 2er0 , 2er6 , 2er7 , 2er9 , 2ewy , 2f3e , 2f3f , 2f3k , 2f80 , 2f81 , 2f8g , 2fdd , 2fde , 2fdp , 2fgu , 2fgv , 2fiv , 2fle , 2fmb , 2fns , 2fnt , 2fs4 , 2fxd , 2fxe , 2g1n , 2g1o , 2g1r , 2g1s , 2g1y , 2g20 , 2g21 , 2g22 , 2g24 , 2g26 , 2g27 , 2g69 , 2g94 , 2h6s , 2h6t , 2hah , 2hb2 , 2hb3 , 2hb4 , 2hc0 , 2hiz , 2hm1 , 2hpe , 2hpf , 2hs1 , 2hs2 , 2hvp , 2i0a , 2i0d , 2i4d , 2i4q , 2i4u , 2i4v , 2i4w , 2i4x , 2idw , 2ien , 2ieo , 2igx , 2igy , 2iqg , 2irz , 2is0 , 2j9j , 2j9k , 2je4 , 2jxr , 2mip , 2nmw , 2nmy , 2nmz , 2nnk , 2nnp , 2nph , 2ntr , 2nxd , 2nxl , 2nxm , 2o40 , 2o4k , 2o4l , 2o4n , 2o4p , 2o4s , 2oah , 2of0 , 2ohk , 2ohl , 2ohm , 2ohn , 2ohp , 2ohq , 2ohr , 2ohs , 2oht , 2ohu , 2p3a , 2p3b , 2p3c , 2p3d , 2p4j , 2p83 , 2p8h , 2pc0 , 2ph6 , 2ph8 , 2pk5 , 2pk6 , 2pqz , 2psg , 2psu , 2psv , 2pwc , 2pym , 2pyn , 2q11 , 2q15 , 2q3k , 2q54 , 2q55 , 2q5k , 2q63 , 2q64 , 2qci , 2qd6 , 2qd7 , 2qd8 , 2qhy , 2qhz , 2qi0 , 2qi1 , 2qi3 , 2qi4 , 2qi5 , 2qi6 , 2qi7 , 2qk5 , 2qmd , 2qmf , 2qmg , 2qmp , 2qnn , 2qnp , 2qnq , 2qp8 , 2qu2 , 2qu3 , 2qzk , 2qzl , 2r5p , 2r5q , 2r9b , 2ren , 2rmp , 2rsp , 2sam , 2upj , 2uxz , 2uy0 , 2v00 , 2va5 , 2va6 , 2va7 , 2vie , 2vij , 2viy , 2viz , 2vj6 , 2vj7 , 2vj9 , 2wea , 2web , 2wec , 2wed , 2z4o , 2zhr , 2zhs , 2zht , 2zhu , 2zhv , 3aid , 3app , 3apr , 3b7v , 3b80 , 3bgb , 3bgc , 3bra , 3buf , 3bug , 3buh , 3bva , 3bvb , 3bxr , 3bxs , 3cib , 3cic , 3cid , 3ckp , 3ckr , 3cms , 3djk , 3ebz , 3ec0 , 3ecg , 3er3 , 3er5 , 3fiv , 3hvp , 3pep , 3phv , 3psg , 3tlh , 3upj , 4ape , 4apr , 4cms , 4er1 , 4er2 , 4er4 , 4fiv , 4hvp , 4pep , 4phv , 4upj , 5apr , 5er1 , 5er2 , 5fiv , 5hvp , 5pep , 5upj , 6apr , 6fiv , 6upj , 7hvp , 7upj , 8hvp , 9hvp
CATH: 2.40.70.10
Database linksHelp
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PDBe-motif: PS00141
Enzyme: EC:3.4.23
PROSITE doc: PDOC00128
MEROPS: A1 , A2

Taxonomic coverageHelp
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Overlapping InterPro entriesHelp
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IPR001969 Numbers of overlapping proteins Average numbers of overlapping amino acids

Example proteinsHelp
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O01530 Aspartic protease 6

P00790 Pepsin A

P00796 Renin-2

P07267 Saccharopepsin

P10394 Retrovirus-related Pol polyprotein from transposon 412

More proteins


Example Proteins Key


InterPro entry accession number/name and structure databases Colour code
IPR012848 Propeptide, peptidase A1
IPR001461 Peptidase A1
IPR015416 Zinc finger, H2C2-type, histone UAS binding
IPR012337 Polynucleotidyl transferase, ribonuclease H fold
IPR000477 RNA-directed DNA polymerase (reverse transcriptase)
IPR001584 Integrase, catalytic core
IPR018061 Peptidase A2A, retrovirus RVP subgroup
IPR001995 Peptidase A2A, retrovirus, catalytic
IPR009007 Peptidase aspartic, catalytic
IPR001969 Peptidase aspartic, active site
PDB Chain
ModBase
CATH Domain
SWISS-MODEL
SCOP Domain

PublicationsHelp
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1. Szecsi PB.
The aspartic proteases.
Scand. J. Clin. Lab. Invest. Suppl. 210 5-22 1992 [PubMed: 1455179]
2. LaPointe CF, Taylor RK.
The type 4 prepilin peptidases comprise a novel family of aspartic acid proteases.
J. Biol. Chem. 275 1502-10 2000 [PubMed: 10625704]
http://dx.doi.org/10.1074/jbc.275.2.1502
3. Ng SY, Chaban B, Jarrell KF.
Archaeal flagella, bacterial flagella and type IV pili: a comparison of genes and posttranslational modifications.
J. Mol. Microbiol. Biotechnol. 11 167-91 2006 [PubMed: 16983194]
http://dx.doi.org/10.1159/000094053
4. Bardy SL, Jarrell KF.
Cleavage of preflagellins by an aspartic acid signal peptidase is essential for flagellation in the archaeon Methanococcus voltae.
Mol. Microbiol. 50 1339-47 2003 [PubMed: 14622420]
http://dx.doi.org/10.1046/j.1365-2958.2003.03758.x

Additional ReadingHelp
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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
Foltmann B.
Gastric proteinases--structure, function, evolution and mechanism of action.
Essays Biochem. 17 1981 52-84 [PubMed: 6795036]
Park H, Min K, Kwak HS, Koo KD, Lim D, Seo SW, Choi JU, Platt B, Choi DY.
Synthesis, SAR, and X-ray structure of human BACE-1 inhibitors with cyclic urea derivatives.
Bioorg. Med. Chem. Lett. 18 2008 2900-4 [PubMed: 18434152]
http://dx.doi.org/10.1016/j.bmcl.2008.03.081
Rao JK, Erickson JW, Wlodawer A.
Structural and evolutionary relationships between retroviral and eucaryotic aspartic proteinases.
Biochemistry 30 1991 4663-71 [PubMed: 1851433]
http://dx.doi.org/10.1021/bi00233a005
Davies DR.
The structure and function of the aspartic proteinases.
19 1990 189-215 [PubMed: 2194475]
Cumming JN, Le TX, Babu S, Carroll C, Chen X, Favreau L, Gaspari P, Guo T, Hobbs DW, Huang Y, Iserloh U, Kennedy ME, Kuvelkar R, Li G, Lowrie J, McHugh NA, Ozgur L, Pan J, Parker EM, Saionz K, Stamford AW, Strickland C, Tadesse D, Voigt J, Wang L, Wu Y, Zhang L, Zhang Q.
Rational design of novel, potent piperazinone and imidazolidinone BACE1 inhibitors.
Bioorg. Med. Chem. Lett. 18 2008 3236-41 [PubMed: 18468890]
http://dx.doi.org/10.1016/j.bmcl.2008.04.050
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
Clarke B, Demont E, Dingwall C, Dunsdon R, Faller A, Hawkins J, Hussain I, MacPherson D, Maile G, Matico R, Milner P, Mosley J, Naylor A, O'Brien A, Redshaw S, Riddell D, Rowland P, Soleil V, Smith KJ, Stanway S, Stemp G, Sweitzer S, Theobald P, Vesey D, Walter DS, Ward J, Wayne G.
BACE-1 inhibitors part 2: identification of hydroxy ethylamines (HEAs) with reduced peptidic character.
Bioorg. Med. Chem. Lett. 18 2008 1017-21 [PubMed: 18166458]
http://dx.doi.org/10.1016/j.bmcl.2007.12.019
Rawlings ND, Barrett AJ.
Families of aspartic peptidases, and those of unknown catalytic mechanism.
Meth. Enzymol. 248 1995 105-20 [PubMed: 7674916]
http://dx.doi.org/10.1016/0076-6879(95)48009-9
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