PPEP2_PAEA2
ID PPEP2_PAEA2 Reviewed; 217 AA.
AC K4ZRC1;
DT 05-DEC-2018, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2013, sequence version 1.
DT 03-AUG-2022, entry version 30.
DE RecName: Full=Pro-Pro endopeptidase {ECO:0000303|PubMed:29794027};
DE Short=PPEP-2 {ECO:0000303|PubMed:29794027};
DE EC=3.4.24.89 {ECO:0000269|PubMed:29794027};
DE Flags: Precursor;
GN ORFNames=PAV_1c07830 {ECO:0000312|EMBL:EJW19796.1};
OS Paenibacillus alvei (strain ATCC 6344 / DSM 29 / NBRC 3343 / NCIMB 9371 /
OS NCTC 6352) (Bacillus alvei).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Paenibacillaceae; Paenibacillus.
OX NCBI_TaxID=1206781;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 6344 / DSM 29 / NBRC 3343 / NCIMB 9371 / NCTC 6352;
RX PubMed=23105091; DOI=10.1128/jb.01698-12;
RA Djukic M., Becker D., Poehlein A., Voget S., Daniel R.;
RT "Genome sequence of Paenibacillus alvei DSM 29, a secondary invader during
RT European foulbrood outbreaks.";
RL J. Bacteriol. 194:6365-6365(2012).
RN [2] {ECO:0007744|PDB:6FPC}
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 28-217, FUNCTION, CATALYTIC
RP ACTIVITY, SUBSTRATE SPECIFICITY, CLEAVAGE MOTIF, COFACTOR, SUBCELLULAR
RP LOCATION, SUBUNIT, IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS OF
RP 112-SER--VAL-115.
RC STRAIN=ATCC 6344 / DSM 29 / NBRC 3343 / NCIMB 9371 / NCTC 6352;
RX PubMed=29794027; DOI=10.1074/jbc.ra118.003244;
RA Klychnikov O.I., Shamorkina T.M., Weeks S.D., van Leeuwen H.C., Corver J.,
RA Drijfhout J.W., van Veelen P.A., Sluchanko N.N., Strelkov S.V.,
RA Hensbergen P.J.;
RT "Discovery of a new Pro-Pro endopeptidase, PPEP-2, provides mechanistic
RT insights into the differences in substrate specificity within the PPEP
RT family.";
RL J. Biol. Chem. 293:11154-11165(2018).
CC -!- FUNCTION: Zinc-dependent endoprotease with a unique preference for
CC proline residues surrounding the scissile bond, which cleaves in a
CC PLP-|-PVP motif. Cleaves the cell surface protein encoded by an
CC adjacent gene, which contains two PPEP-2 cleaving sites and putative
CC extracellular matrix-binding domains. Thereby, may have a role in the
CC regulation of P.alvei adhesion. Is not able to cleave within the PVP-|-
CC PVQ motif, and only shows a very poor cleavage of the VNP-|-PVP motif
CC in vitro, which is the optimal substrate peptide for PPEP-1 from
CC P.difficile. {ECO:0000269|PubMed:29794027}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=The enzyme catalyzes the hydrolytic cleavage of peptide bonds
CC between two proline residues.; EC=3.4.24.89;
CC Evidence={ECO:0000269|PubMed:29794027};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU01339,
CC ECO:0000269|PubMed:29794027};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|PROSITE-
CC ProRule:PRU01339, ECO:0000269|PubMed:29794027};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=70 uM for a FRET peptide containing PLPPVP
CC {ECO:0000269|PubMed:29794027};
CC KM=330 uM for a FRET peptide containing VLPPVP
CC {ECO:0000269|PubMed:29794027};
CC Note=kcat is 8 sec(-1) with a FRET peptide containing PLPPVP as
CC substrate. kcat is 3 sec(-1) with a FRET peptide containing VLPPVP as
CC substrate. {ECO:0000269|PubMed:29794027};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:29794027}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:29794027}.
CC -!- SIMILARITY: Belongs to the peptidase M34 family. Pro-Pro endopeptidase
CC subfamily. {ECO:0000305}.
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DR EMBL; AMBZ01000001; EJW19796.1; -; Genomic_DNA.
DR RefSeq; WP_005543643.1; NZ_AMBZ01000001.1.
DR PDB; 6FPC; X-ray; 1.75 A; A/B/C/D=28-217.
DR PDBsum; 6FPC; -.
DR AlphaFoldDB; K4ZRC1; -.
DR SMR; K4ZRC1; -.
DR MEROPS; M34.003; -.
DR EnsemblBacteria; EJW19796; EJW19796; PAV_1c07830.
DR PATRIC; fig|1206781.3.peg.795; -.
DR OrthoDB; 1305971at2; -.
DR BRENDA; 3.4.24.89; 629.
DR Proteomes; UP000006321; Unassembled WGS sequence.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008237; F:metallopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR PROSITE; PS51995; ATLF; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydrolase; Metal-binding; Metalloprotease; Protease;
KW Secreted; Signal; Zinc.
FT SIGNAL 1..27
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29794027"
FT CHAIN 28..217
FT /note="Pro-Pro endopeptidase"
FT /id="PRO_5003881148"
FT DOMAIN 30..216
FT /note="ATLF-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01339"
FT REGION 112..115
FT /note="Plays a crucial role in substrate specificity"
FT /evidence="ECO:0000269|PubMed:29794027"
FT ACT_SITE 138
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01339"
FT BINDING 137
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01339,
FT ECO:0000269|PubMed:29794027"
FT BINDING 141
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01339,
FT ECO:0000269|PubMed:29794027"
FT BINDING 174
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01339,
FT ECO:0000269|PubMed:29794027"
FT BINDING 181
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01339,
FT ECO:0000269|PubMed:29794027"
FT SITE 174
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250|UniProtKB:Q183R7"
FT MUTAGEN 112..115
FT /note="SERV->GGST: Displays a shift in substrate
FT specificity toward PPEP-1 substrates."
FT /evidence="ECO:0000269|PubMed:29794027"
FT HELIX 33..36
FT /evidence="ECO:0007829|PDB:6FPC"
FT HELIX 46..56
FT /evidence="ECO:0007829|PDB:6FPC"
FT HELIX 61..69
FT /evidence="ECO:0007829|PDB:6FPC"
FT STRAND 73..79
FT /evidence="ECO:0007829|PDB:6FPC"
FT HELIX 81..83
FT /evidence="ECO:0007829|PDB:6FPC"
FT HELIX 85..90
FT /evidence="ECO:0007829|PDB:6FPC"
FT TURN 99..102
FT /evidence="ECO:0007829|PDB:6FPC"
FT HELIX 105..107
FT /evidence="ECO:0007829|PDB:6FPC"
FT STRAND 109..119
FT /evidence="ECO:0007829|PDB:6FPC"
FT STRAND 127..129
FT /evidence="ECO:0007829|PDB:6FPC"
FT HELIX 134..146
FT /evidence="ECO:0007829|PDB:6FPC"
FT STRAND 148..150
FT /evidence="ECO:0007829|PDB:6FPC"
FT HELIX 151..153
FT /evidence="ECO:0007829|PDB:6FPC"
FT HELIX 155..164
FT /evidence="ECO:0007829|PDB:6FPC"
FT HELIX 166..169
FT /evidence="ECO:0007829|PDB:6FPC"
FT TURN 175..177
FT /evidence="ECO:0007829|PDB:6FPC"
FT HELIX 179..192
FT /evidence="ECO:0007829|PDB:6FPC"
FT HELIX 194..203
FT /evidence="ECO:0007829|PDB:6FPC"
FT HELIX 205..214
FT /evidence="ECO:0007829|PDB:6FPC"
SQ SEQUENCE 217 AA; 24015 MW; 265AE6908E376AF5 CRC64;
MKWDKRVVAL ILAVMIVCPL FAAPAHAQEQ SILDKLVVLP SGEYNHSEAA AMKQRLEKIP
TSILDALYSK GVKIKLTQGA ITNEPELAYL KGVVPRGWEG TGLTWDDVPG VSERVVAVRI
GYSEKGKGHN SLNLEIHETL HAVDRLVLNE VSGTDEFINI FNKEASVKYK GDGYVSAYPT
EYFAEAASLY LYSDATRSDL KDSMPLTYEF MAKLFAN
