PEPQ_ALTSX
ID PEPQ_ALTSX Reviewed; 517 AA.
AC Q44238;
DT 21-AUG-2007, integrated into UniProtKB/Swiss-Prot.
DT 15-JAN-2008, sequence version 3.
DT 03-AUG-2022, entry version 96.
DE RecName: Full=Xaa-Pro dipeptidase;
DE Short=X-Pro dipeptidase;
DE EC=3.4.13.9;
DE AltName: Full=DFPase;
DE AltName: Full=Imidodipeptidase;
DE AltName: Full=Organophosphorus acid anhydrolase 2;
DE Short=OPAA-2;
DE EC=3.1.8.2;
DE AltName: Full=Paraoxon hydrolase;
DE AltName: Full=Phosphotriesterase;
DE EC=3.1.8.1;
DE AltName: Full=Proline dipeptidase;
DE Short=Prolidase;
GN Name=pepQ; Synonyms=opaA;
OS Alteromonas sp.
OC Bacteria; Proteobacteria; Gammaproteobacteria; Alteromonadales;
OC Alteromonadaceae; Alteromonas/Salinimonas group; Alteromonas.
OX NCBI_TaxID=232;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, COFACTOR, AND
RP BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=JD6.5;
RX PubMed=8633861; DOI=10.1128/aem.62.5.1636-1641.1996;
RA Cheng T.-C., Harvey S.P., Chen G.L.;
RT "Cloning and expression of a gene encoding a bacterial enzyme for
RT decontamination of organophosphorus nerve agents and nucleotide sequence of
RT the enzyme.";
RL Appl. Environ. Microbiol. 62:1636-1641(1996).
RN [2]
RP FUNCTION, SUBUNIT, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC STRAIN=JD6.5;
RX PubMed=2001997; DOI=10.1128/jb.173.6.1938-1943.1991;
RA DeFrank J.J., Cheng T.-C.;
RT "Purification and properties of an organophosphorus acid anhydrase from a
RT halophilic bacterial isolate.";
RL J. Bacteriol. 173:1938-1943(1991).
RN [3]
RP FUNCTION.
RC STRAIN=JD6.5;
RX PubMed=9079288; DOI=10.1038/sj.jim.2900358;
RA Cheng T.-C., Liu L., Wang B., Wu J., DeFrank J.J., Anderson D.M.,
RA Rastogi V.K., Hamilton A.B.;
RT "Nucleotide sequence of a gene encoding an organophosphorus nerve agent
RT degrading enzyme from Alteromonas haloplanktis.";
RL J. Ind. Microbiol. Biotechnol. 18:49-55(1997).
RN [4]
RP FUNCTION, SUBSTRATE SPECIFICITY, AND STEREOSELECTIVITY.
RC STRAIN=JD6.5;
RX PubMed=10866401; DOI=10.1016/s0960-894x(00)00213-4;
RA Hill C.M., Wu F., Cheng T.-C., DeFrank J.J., Raushel F.M.;
RT "Substrate and stereochemical specificity of the organophosphorus acid
RT anhydrolase from Alteromonas sp. JD6.5 toward p-nitrophenyl
RT phosphotriesters.";
RL Bioorg. Med. Chem. Lett. 10:1285-1288(2000).
RN [5]
RP STEREOSELECTIVITY.
RX PubMed=11300693; DOI=10.1006/bioo.2000.1189;
RA Hill C.M., Li W.-S., Cheng T.-C., DeFrank J.J., Raushel F.M.;
RT "Stereochemical specificity of organophosphorus acid anhydrolase toward p-
RT nitrophenyl analogs of soman and sarin.";
RL Bioorg. Chem. 29:27-35(2001).
CC -!- FUNCTION: Splits dipeptides with a prolyl or hydroxyprolyl residue in
CC the C-terminal position and a nonpolar amino acid at the N-terminal
CC position. Also catalyzes the hydrolysis of toxic organophosphorus
CC cholinesterase-inhibiting compounds including insecticide paraoxon and
CC nerve gases such as diisopropylfluorophosphate (DFP), O-isopropyl
CC methylphosphonofluoridate (sarin), O-pinacolyl
CC methylphosphonofluoridate (soman), and O-cyclohexyl
CC methylphosphonofluoridate. {ECO:0000269|PubMed:10866401,
CC ECO:0000269|PubMed:2001997, ECO:0000269|PubMed:8633861,
CC ECO:0000269|PubMed:9079288}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of Xaa-|-Pro dipeptides. Also acts on aminoacyl-
CC hydroxyproline analogs. No action on Pro-|-Pro.; EC=3.4.13.9;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=diisopropyl fluorophosphate + H2O = diisopropyl phosphate +
CC fluoride + 2 H(+); Xref=Rhea:RHEA:24100, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17051, ChEBI:CHEBI:17941,
CC ChEBI:CHEBI:57896; EC=3.1.8.2;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=An aryl dialkyl phosphate + H2O = dialkyl phosphate + an aryl
CC alcohol.; EC=3.1.8.1;
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:8633861};
CC Note=Binds 2 manganese ions per monomer. {ECO:0000269|PubMed:8633861};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=2.99 mM for diisopropylfluorophosphate
CC {ECO:0000269|PubMed:2001997, ECO:0000269|PubMed:8633861};
CC KM=1.57 mM for O-isopropyl methylphosphonofluoridate
CC {ECO:0000269|PubMed:2001997, ECO:0000269|PubMed:8633861};
CC KM=2.48 mM for O-pinacolyl methylphosphonofluoridate
CC {ECO:0000269|PubMed:2001997, ECO:0000269|PubMed:8633861};
CC KM=0.63 mM for O-cyclohexyl methylphosphonofluoridate
CC {ECO:0000269|PubMed:2001997, ECO:0000269|PubMed:8633861};
CC KM=1.27 mM for a chromogenic soman analog
CC {ECO:0000269|PubMed:2001997, ECO:0000269|PubMed:8633861};
CC Vmax=230 umol/min/mg enzyme with diisopropylfluorophosphate as
CC substrate {ECO:0000269|PubMed:2001997, ECO:0000269|PubMed:8633861};
CC Vmax=442 umol/min/mg enzyme with O-isopropyl
CC methylphosphonofluoridate as substrate {ECO:0000269|PubMed:2001997,
CC ECO:0000269|PubMed:8633861};
CC Vmax=151 umol/min/mg enzyme with O-pinacolyl
CC methylphosphonofluoridate as substrate {ECO:0000269|PubMed:2001997,
CC ECO:0000269|PubMed:8633861};
CC Vmax=652 umol/min/mg enzyme with O-cyclohexyl
CC methylphosphonofluoridate as substrate {ECO:0000269|PubMed:2001997,
CC ECO:0000269|PubMed:8633861};
CC Vmax=52 umol/min/mg enzyme with a chromogenic soman analog as
CC substrate {ECO:0000269|PubMed:2001997, ECO:0000269|PubMed:8633861};
CC pH dependence:
CC Optimum pH is 8.5 with DFP as substrate. {ECO:0000269|PubMed:2001997,
CC ECO:0000269|PubMed:8633861};
CC Temperature dependence:
CC Optimum temperature is 50 degrees Celsius.
CC {ECO:0000269|PubMed:2001997, ECO:0000269|PubMed:8633861};
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:2001997}.
CC -!- BIOTECHNOLOGY: Can be used for the catalytic detoxification of some
CC nerve agents neurotoxins.
CC -!- MISCELLANEOUS: Has a stereoselective preference for isomers with R-
CC configuration at the phosphorous center of sarin and soman, and with S-
CC configuration in phosphotriesters.
CC -!- SIMILARITY: Belongs to the peptidase M24B family. Bacterial-type
CC prolidase subfamily. {ECO:0000305}.
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DR EMBL; U29240; AAB05590.1; -; Genomic_DNA.
DR PDB; 3L24; X-ray; 2.30 A; A/B/C=1-517.
DR PDB; 3L7G; X-ray; 2.70 A; A/B/C=1-517.
DR PDB; 4ZWO; X-ray; 2.14 A; A/B=1-437.
DR PDB; 4ZWP; X-ray; 2.40 A; A/B=1-437.
DR PDB; 4ZWU; X-ray; 2.20 A; A/B=1-437.
DR PDBsum; 3L24; -.
DR PDBsum; 3L7G; -.
DR PDBsum; 4ZWO; -.
DR PDBsum; 4ZWP; -.
DR PDBsum; 4ZWU; -.
DR AlphaFoldDB; Q44238; -.
DR SMR; Q44238; -.
DR ChEMBL; CHEMBL4252; -.
DR MEROPS; M24.003; -.
DR BioCyc; MetaCyc:MON-7712; -.
DR BRENDA; 3.1.8.2; 275.
DR EvolutionaryTrace; Q44238; -.
DR GO; GO:0004063; F:aryldialkylphosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0047862; F:diisopropyl-fluorophosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008235; F:metalloexopeptidase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0102009; F:proline dipeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR GO; GO:0009636; P:response to toxic substance; IEA:UniProtKB-KW.
DR Gene3D; 3.40.350.10; -; 1.
DR Gene3D; 3.90.230.10; -; 1.
DR HAMAP; MF_01279; X_Pro_dipeptid; 1.
DR InterPro; IPR029149; Creatin/AminoP/Spt16_NTD.
DR InterPro; IPR036005; Creatinase/aminopeptidase-like.
DR InterPro; IPR000994; Pept_M24.
DR InterPro; IPR001131; Peptidase_M24B_aminopep-P_CS.
DR InterPro; IPR022846; X_Pro_dipept.
DR Pfam; PF00557; Peptidase_M24; 1.
DR SUPFAM; SSF55920; SSF55920; 1.
DR PROSITE; PS00491; PROLINE_PEPTIDASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Detoxification; Dipeptidase; Hydrolase; Manganese;
KW Metal-binding; Metalloprotease; Protease.
FT CHAIN 1..517
FT /note="Xaa-Pro dipeptidase"
FT /id="PRO_0000298944"
FT BINDING 244
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 255
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 255
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 336
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 381
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 420
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 420
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT HELIX 3..25
FT /evidence="ECO:0007829|PDB:4ZWO"
FT STRAND 29..34
FT /evidence="ECO:0007829|PDB:4ZWO"
FT HELIX 54..57
FT /evidence="ECO:0007829|PDB:4ZWO"
FT STRAND 69..72
FT /evidence="ECO:0007829|PDB:4ZWO"
FT STRAND 74..76
FT /evidence="ECO:0007829|PDB:4ZWO"
FT STRAND 79..83
FT /evidence="ECO:0007829|PDB:4ZWO"
FT STRAND 88..90
FT /evidence="ECO:0007829|PDB:3L24"
FT HELIX 99..103
FT /evidence="ECO:0007829|PDB:4ZWO"
FT STRAND 104..111
FT /evidence="ECO:0007829|PDB:4ZWO"
FT HELIX 112..117
FT /evidence="ECO:0007829|PDB:4ZWO"
FT HELIX 123..125
FT /evidence="ECO:0007829|PDB:4ZWP"
FT STRAND 126..131
FT /evidence="ECO:0007829|PDB:4ZWO"
FT HELIX 133..139
FT /evidence="ECO:0007829|PDB:4ZWO"
FT STRAND 143..145
FT /evidence="ECO:0007829|PDB:4ZWO"
FT HELIX 147..156
FT /evidence="ECO:0007829|PDB:4ZWO"
FT HELIX 162..187
FT /evidence="ECO:0007829|PDB:4ZWO"
FT HELIX 192..203
FT /evidence="ECO:0007829|PDB:4ZWO"
FT HELIX 207..209
FT /evidence="ECO:0007829|PDB:4ZWO"
FT STRAND 210..212
FT /evidence="ECO:0007829|PDB:4ZWO"
FT STRAND 215..218
FT /evidence="ECO:0007829|PDB:4ZWO"
FT HELIX 219..223
FT /evidence="ECO:0007829|PDB:4ZWO"
FT STRAND 240..245
FT /evidence="ECO:0007829|PDB:4ZWO"
FT STRAND 256..264
FT /evidence="ECO:0007829|PDB:4ZWO"
FT HELIX 267..283
FT /evidence="ECO:0007829|PDB:4ZWO"
FT HELIX 292..309
FT /evidence="ECO:0007829|PDB:4ZWO"
FT STRAND 312..315
FT /evidence="ECO:0007829|PDB:4ZWO"
FT HELIX 317..322
FT /evidence="ECO:0007829|PDB:4ZWO"
FT TURN 323..325
FT /evidence="ECO:0007829|PDB:4ZWU"
FT HELIX 326..329
FT /evidence="ECO:0007829|PDB:4ZWO"
FT STRAND 334..337
FT /evidence="ECO:0007829|PDB:4ZWP"
FT STRAND 339..343
FT /evidence="ECO:0007829|PDB:4ZWO"
FT STRAND 347..351
FT /evidence="ECO:0007829|PDB:4ZWU"
FT STRAND 376..380
FT /evidence="ECO:0007829|PDB:4ZWO"
FT STRAND 383..385
FT /evidence="ECO:0007829|PDB:4ZWO"
FT HELIX 388..395
FT /evidence="ECO:0007829|PDB:4ZWO"
FT TURN 396..399
FT /evidence="ECO:0007829|PDB:3L7G"
FT HELIX 400..402
FT /evidence="ECO:0007829|PDB:4ZWO"
FT HELIX 405..411
FT /evidence="ECO:0007829|PDB:4ZWO"
FT HELIX 412..414
FT /evidence="ECO:0007829|PDB:4ZWO"
FT STRAND 416..418
FT /evidence="ECO:0007829|PDB:4ZWO"
FT STRAND 420..425
FT /evidence="ECO:0007829|PDB:4ZWO"
FT STRAND 430..432
FT /evidence="ECO:0007829|PDB:4ZWO"
FT HELIX 433..436
FT /evidence="ECO:0007829|PDB:4ZWO"
SQ SEQUENCE 517 AA; 58998 MW; 9B92D811445C72A3 CRC64;
MNKLAVLYAE HIATLQKRTR EIIERENLDG VVFHSGQAKR QFLDDMYYPF KVNPQFKAWL
PVIDNPHCWI VANGTDKPKL IFYRPVDFWH KVPDEPNEYW ADYFDIELLV KPDQVEKLLP
YDKARFAYIG EYLEVAQALG FELMNPEPVM NFYHYHRAYK TQYELACMRE ANKIAVQGHK
AARDAFFQGK SEFEIQQAYL LATQHSENDN AYGNIVALNE NCAILHYTHF DRVAPATHRS
FLIDAGANFN GYAADITRTY DFTGEGEFAE LVATMKQHQI ALCNQLAPGK LYGELHLDCH
QRVAQTLSDF NIVDLSADEI VAKGITSTFF PHGLGHHIGL QVHDVGGFMA DEQGAHQEPP
EGHPFLRCTR KIEANQVFTI EPGLYFIDSL LGDLAATDNN QHINWDKVAE LKPFGGIRIE
DNIIVHEDSL ENMTRELRAR LTTHSLRGLS APQFSINDPA VMSEYSYPSE PLSYEEEIKK
STFIVHVRTR RILVRRRTLS PILIAVTPMP AITAGLM
