PEPA1_PENJA
ID PEPA1_PENJA Reviewed; 323 AA.
AC P00798;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1998, sequence version 2.
DT 03-AUG-2022, entry version 116.
DE RecName: Full=Penicillopepsin-1 {ECO:0000305|PubMed:4946839};
DE EC=3.4.23.20 {ECO:0000269|PubMed:4946839};
DE AltName: Full=Aspartic protease;
DE AltName: Full=Peptidase A;
OS Penicillium janthinellum (Penicillium vitale).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=5079;
RN [1]
RP PROTEIN SEQUENCE, AND X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX PubMed=323722; DOI=10.1038/266140a0;
RA Hsu I.N., Delbaere L.T., James M.N., Hofmann T.;
RT "Penicillopepsin from Penicillium janthinellum crystal structure at 2.8 A
RT and sequence homology with porcine pepsin.";
RL Nature 266:140-145(1977).
RN [2]
RP PARTIAL PROTEIN SEQUENCE.
RX PubMed=825204; DOI=10.1139/o76-128;
RA Cunningham A., Wang H.M., Jones S.R., Chiericato G., Rao L., Harris C.I.,
RA Rhee S.H., Hofmann T.;
RT "Amino acid sequence of penicillopepsin. IV. Myxobacter AL-1 protease II
RT and Staphylococcus aureus protease fragments and homology with pig pepsin
RT and chymosin.";
RL Can. J. Biochem. 54:902-914(1976).
RN [3]
RP PROTEIN SEQUENCE, X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS), AND DISULFIDE
RP BONDS.
RX PubMed=6341600; DOI=10.1016/0022-2836(83)90008-6;
RA James M.N.G., Sielecki A.R.;
RT "Structure and refinement of penicillopepsin at 1.8-A resolution.";
RL J. Mol. Biol. 163:299-361(1983).
RN [4]
RP ACTIVE SITE.
RX PubMed=5475460; DOI=10.1139/o70-158;
RA Sodek J., Hofmann T.;
RT "Amino acid sequence around the active site aspartic acid in
RT penicillopepsin.";
RL Can. J. Biochem. 48:1014-1016(1970).
RN [5]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBSTRATE SPECIFICITY.
RX PubMed=4946839; DOI=10.1139/o71-164;
RA Mains G., Takahashi M., Sodek J., Hofmann T.;
RT "The specificity of penicillopepsin.";
RL Can. J. Biochem. 49:1134-1149(1971).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (0.95 ANGSTROMS), GLYCOSYLATION AT SER-3 AND THR-7,
RP AND DISULFIDE BONDS.
RX PubMed=9836576; DOI=10.1021/bi9821364;
RA Khan A.R., Parrish J.C., Fraser M.E., Smith W.W., Bartlett P.A.,
RA James M.N.G.;
RT "Lowering the entropic barrier for binding conformationally flexible
RT inhibitors to enzymes.";
RL Biochemistry 37:16839-16845(1998).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS), GLYCOSYLATION AT SER-3 AND THR-7,
RP AND DISULFIDE BONDS.
RX DOI=10.1021/ja973714r;
RA Ding J., Fraser M.E., Meyer J.H., Bartlett P.A., James M.N.G.;
RT "Macrocyclic inhibitors of penicillopepsin. II. X-Ray crystallographic
RT analyses of penicillopepsin complexed with a P3-P1 macrocyclic peptidyl
RT inhibitor and with its two acyclic analogues.";
RL J. Am. Chem. Soc. 120:4610-4621(1998).
CC -!- FUNCTION: Secreted aspartic endopeptidase that allows assimilation of
CC proteinaceous substrates. The scissile peptide bond is attacked by a
CC nucleophilic water molecule activated by two aspartic residues in the
CC active site. Shows a broad primary substrate specificity. Favors
CC hydrophobic residues at the P1 and P1' positions, but can also activate
CC trypsinogen and hydrolyze the B chain of insulin between positions
CC 'Gly-20' and 'Glu-21'. {ECO:0000269|PubMed:4946839}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of proteins with broad specificity similar to that
CC of pepsin A, preferring hydrophobic residues at P1 and P1', but also
CC cleaving 20-Gly-|-Glu-21 in the B chain of insulin. Clots milk, and
CC activates trypsinogen.; EC=3.4.23.20;
CC Evidence={ECO:0000269|PubMed:4946839};
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q12567}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q01972}.
CC -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000255|PROSITE-
CC ProRule:PRU01103}.
CC -!- CAUTION: The sequence shown is derived from the best amino acid
CC sequence data as modified by the X-ray data. {ECO:0000305}.
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DR PIR; A00991; PEPLBJ.
DR PDB; 1APT; X-ray; 1.80 A; E=1-323.
DR PDB; 1APU; X-ray; 1.80 A; E=1-323.
DR PDB; 1APV; X-ray; 1.80 A; E=1-323.
DR PDB; 1APW; X-ray; 1.80 A; E=1-323.
DR PDB; 1BXO; X-ray; 0.95 A; A=1-323.
DR PDB; 1BXQ; X-ray; 1.41 A; A=1-323.
DR PDB; 1PPK; X-ray; 1.80 A; E=1-323.
DR PDB; 1PPL; X-ray; 1.70 A; E=1-323.
DR PDB; 1PPM; X-ray; 1.70 A; E=1-323.
DR PDB; 2WEA; X-ray; 1.25 A; A=1-323.
DR PDB; 2WEB; X-ray; 1.50 A; A=1-323.
DR PDB; 2WEC; X-ray; 1.50 A; A=1-323.
DR PDB; 2WED; X-ray; 1.50 A; A=1-323.
DR PDB; 3APP; X-ray; 1.80 A; A=1-323.
DR PDBsum; 1APT; -.
DR PDBsum; 1APU; -.
DR PDBsum; 1APV; -.
DR PDBsum; 1APW; -.
DR PDBsum; 1BXO; -.
DR PDBsum; 1BXQ; -.
DR PDBsum; 1PPK; -.
DR PDBsum; 1PPL; -.
DR PDBsum; 1PPM; -.
DR PDBsum; 2WEA; -.
DR PDBsum; 2WEB; -.
DR PDBsum; 2WEC; -.
DR PDBsum; 2WED; -.
DR PDBsum; 3APP; -.
DR AlphaFoldDB; P00798; -.
DR SMR; P00798; -.
DR BindingDB; P00798; -.
DR ChEMBL; CHEMBL4254; -.
DR MEROPS; A01.011; -.
DR iPTMnet; P00798; -.
DR BRENDA; 3.4.23.20; 4621.
DR EvolutionaryTrace; P00798; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR CDD; cd06097; Aspergillopepsin_like; 1.
DR Gene3D; 2.40.70.10; -; 2.
DR InterPro; IPR001461; Aspartic_peptidase_A1.
DR InterPro; IPR001969; Aspartic_peptidase_AS.
DR InterPro; IPR034163; Aspergillopepsin-like_cat_dom.
DR InterPro; IPR033121; PEPTIDASE_A1.
DR InterPro; IPR021109; Peptidase_aspartic_dom_sf.
DR PANTHER; PTHR47966; PTHR47966; 1.
DR Pfam; PF00026; Asp; 1.
DR PRINTS; PR00792; PEPSIN.
DR SUPFAM; SSF50630; SSF50630; 1.
DR PROSITE; PS00141; ASP_PROTEASE; 2.
DR PROSITE; PS51767; PEPTIDASE_A1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Aspartyl protease; Direct protein sequencing; Disulfide bond;
KW Glycoprotein; Hydrolase; Protease; Secreted.
FT CHAIN 1..323
FT /note="Penicillopepsin-1"
FT /id="PRO_0000199515"
FT DOMAIN 17..320
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT ACT_SITE 33
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103,
FT ECO:0000269|PubMed:5475460"
FT ACT_SITE 213
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103,
FT ECO:0000269|PubMed:5475460"
FT CARBOHYD 3
FT /note="O-linked (Man...) serine"
FT /evidence="ECO:0000269|PubMed:9836576, ECO:0000269|Ref.7"
FT CARBOHYD 7
FT /note="O-linked (Man...) threonine"
FT /evidence="ECO:0000269|PubMed:9836576, ECO:0000269|Ref.7"
FT DISULFID 249..283
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103,
FT ECO:0000269|PubMed:6341600, ECO:0000269|PubMed:9836576,
FT ECO:0000269|Ref.7"
FT CONFLICT 253
FT /note="L -> V (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 296
FT /note="S -> L (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 4..10
FT /evidence="ECO:0007829|PDB:1BXO"
FT HELIX 12..14
FT /evidence="ECO:0007829|PDB:1BXO"
FT STRAND 17..23
FT /evidence="ECO:0007829|PDB:1BXO"
FT STRAND 26..33
FT /evidence="ECO:0007829|PDB:1BXO"
FT STRAND 39..41
FT /evidence="ECO:0007829|PDB:1BXO"
FT HELIX 48..51
FT /evidence="ECO:0007829|PDB:1BXO"
FT HELIX 59..62
FT /evidence="ECO:0007829|PDB:1BXO"
FT STRAND 64..74
FT /evidence="ECO:0007829|PDB:1BXO"
FT STRAND 80..92
FT /evidence="ECO:0007829|PDB:1BXO"
FT STRAND 95..108
FT /evidence="ECO:0007829|PDB:1BXO"
FT HELIX 110..113
FT /evidence="ECO:0007829|PDB:1BXO"
FT STRAND 119..123
FT /evidence="ECO:0007829|PDB:1BXO"
FT HELIX 127..129
FT /evidence="ECO:0007829|PDB:1BXO"
FT STRAND 133..135
FT /evidence="ECO:0007829|PDB:1BXO"
FT HELIX 140..144
FT /evidence="ECO:0007829|PDB:1BXO"
FT HELIX 145..147
FT /evidence="ECO:0007829|PDB:1BXO"
FT STRAND 148..156
FT /evidence="ECO:0007829|PDB:1BXO"
FT STRAND 159..161
FT /evidence="ECO:0007829|PDB:1BXO"
FT STRAND 163..169
FT /evidence="ECO:0007829|PDB:1BXO"
FT HELIX 172..174
FT /evidence="ECO:0007829|PDB:1BXO"
FT STRAND 175..177
FT /evidence="ECO:0007829|PDB:1BXO"
FT STRAND 180..183
FT /evidence="ECO:0007829|PDB:1BXO"
FT STRAND 192..200
FT /evidence="ECO:0007829|PDB:1BXO"
FT STRAND 203..212
FT /evidence="ECO:0007829|PDB:1BXO"
FT STRAND 217..221
FT /evidence="ECO:0007829|PDB:1BXO"
FT HELIX 223..230
FT /evidence="ECO:0007829|PDB:1BXO"
FT STRAND 237..239
FT /evidence="ECO:0007829|PDB:1BXO"
FT TURN 240..243
FT /evidence="ECO:0007829|PDB:1BXO"
FT STRAND 244..247
FT /evidence="ECO:0007829|PDB:1BXO"
FT STRAND 256..260
FT /evidence="ECO:0007829|PDB:1BXO"
FT STRAND 263..267
FT /evidence="ECO:0007829|PDB:1BXO"
FT HELIX 269..272
FT /evidence="ECO:0007829|PDB:1BXO"
FT STRAND 273..276
FT /evidence="ECO:0007829|PDB:1BXO"
FT STRAND 278..281
FT /evidence="ECO:0007829|PDB:1BXO"
FT STRAND 283..289
FT /evidence="ECO:0007829|PDB:1BXO"
FT STRAND 294..298
FT /evidence="ECO:0007829|PDB:1BXO"
FT HELIX 300..303
FT /evidence="ECO:0007829|PDB:1BXO"
FT STRAND 306..311
FT /evidence="ECO:0007829|PDB:1BXO"
FT TURN 312..315
FT /evidence="ECO:0007829|PDB:1BXO"
FT STRAND 316..322
FT /evidence="ECO:0007829|PDB:1BXO"
SQ SEQUENCE 323 AA; 33461 MW; B4124268364CBA3B CRC64;
AASGVATNTP TANDEEYITP VTIGGTTLNL NFDTGSADLW VFSTELPASQ QSGHSVYNPS
ATGKELSGYT WSISYGDGSS ASGNVFTDSV TVGGVTAHGQ AVQAAQQISA QFQQDTNNDG
LLGLAFSSIN TVQPQSQTTF FDTVKSSLAQ PLFAVALKHQ QPGVYDFGFI DSSKYTGSLT
YTGVDNSQGF WSFNVDSYTA GSQSGDGFSG IADTGTTLLL LDDSVVSQYY SQVSGAQQDS
NAGGYVFDCS TNLPDFSVSI SGYTATVPGS LINYGPSGDG STCLGGIQSN SGIGFSIFGD
IFLKSQYVVF DSDGPQLGFA PQA
