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 27-MAR-2024, entry version 102. 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; Pseudomonadota; 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=H2O + Xaa-L-Pro dipeptide = an L-alpha-amino acid + L-proline; CC Xref=Rhea:RHEA:76407, ChEBI:CHEBI:15377, ChEBI:CHEBI:59869, CC ChEBI:CHEBI:60039, ChEBI:CHEBI:195196; 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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:MONOMER-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 CDD; cd01087; Prolidase; 1. DR Gene3D; 3.90.230.10; Creatinase/methionine aminopeptidase superfamily; 1. DR Gene3D; 3.40.350.10; Creatinase/prolidase N-terminal domain; 1. DR HAMAP; MF_01279; X_Pro_dipeptid; 1. DR InterPro; IPR029149; Creatin/AminoP/Spt16_NTD. DR InterPro; IPR036005; Creatinase/aminopeptidase-like. DR InterPro; IPR048819; PepQ_N. DR InterPro; IPR000994; Pept_M24. DR InterPro; IPR001131; Peptidase_M24B_aminopep-P_CS. DR InterPro; IPR022846; X_Pro_dipept. DR PANTHER; PTHR43226; XAA-PRO AMINOPEPTIDASE 3; 1. DR PANTHER; PTHR43226:SF4; XAA-PRO AMINOPEPTIDASE 3; 1. DR Pfam; PF21216; PepQ_N; 1. DR Pfam; PF00557; Peptidase_M24; 1. DR SUPFAM; SSF55920; Creatinase/aminopeptidase; 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 //