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Protein

Isoaspartyl dipeptidase

Gene

iadA

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the hydrolytic cleavage of a subset of L-isoaspartyl (L-beta-aspartyl) dipeptides. Used to degrade proteins damaged by L-isoaspartyl residues formation. The best substrate for the enzyme reported thus far is iso-Asp-Leu.4 Publications

Cofactori

Zn2+3 Publications, Co2+3 PublicationsNote: Binds 2 Zn(2+) ions per subunit. Has highest activity with Zn(2+) ions, but is also active with Co2+ ions.3 Publications

Enzyme regulationi

P-hydroxymercuribenzoate causes a slight inhibition (8 to 17 %). Iodoacetamide, o-iodosobenzoate and ammonium persulfate do not inhibit the enzyme activity.1 Publication

Kineticsi

  1. KM=0.81 mM for beta-aspartylleucine (at pH 8.0)1 Publication

    pH dependencei

    Optimum pH is 7.5. Active over a wide pH range.1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi68 – 681Zinc 1; via tele nitrogen; catalytic
    Metal bindingi70 – 701Zinc 1; via tele nitrogen; catalytic
    Binding sitei106 – 1061Substrate
    Binding sitei137 – 1371Substrate
    Metal bindingi162 – 1621Zinc 1; via carbamate group; catalytic
    Metal bindingi162 – 1621Zinc 2; via carbamate group; catalytic
    Binding sitei169 – 1691Substrate
    Metal bindingi201 – 2011Zinc 2; via pros nitrogen; catalytic
    Metal bindingi230 – 2301Zinc 2; via tele nitrogen; catalytic
    Binding sitei233 – 2331Substrate
    Active sitei285 – 2851Proton acceptor1 Publication
    Metal bindingi285 – 2851Zinc 1; catalytic
    Binding sitei289 – 2891Substrate; via amide nitrogen and carbonyl oxygen

    GO - Molecular functioni

    • beta-aspartyl-peptidase activity Source: UniProtKB
    • hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds Source: InterPro
    • metallopeptidase activity Source: UniProtKB-KW
    • zinc ion binding Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Hydrolase, Metalloprotease, Protease

    Keywords - Ligandi

    Cobalt, Metal-binding, Zinc

    Enzyme and pathway databases

    BioCyciEcoCyc:G7925-MONOMER.
    ECOL316407:JW4291-MONOMER.
    MetaCyc:G7925-MONOMER.
    BRENDAi3.4.19.5. 2026.
    SABIO-RKP39377.

    Protein family/group databases

    MEROPSiM38.001.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Isoaspartyl dipeptidase (EC:3.4.19.-)
    Gene namesi
    Name:iadA
    Synonyms:yjiF
    Ordered Locus Names:b4328, JW4291
    OrganismiEscherichia coli (strain K12)
    Taxonomic identifieri83333 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
    ProteomesiUP000000318 Componenti: Chromosome UP000000625 Componenti: Chromosome

    Organism-specific databases

    EcoGeneiEG12567. iadA.

    Subcellular locationi

    GO - Cellular componenti

    • cytoplasm Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Disruption phenotypei

    No observable phenotype. Does not result in reduced stationary phase or heat shock survival. Approximately 31% of the enzyme activity present.1 Publication

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi77 – 771E → D or Q: Reduces activity 100000-fold. 2 Publications
    Mutagenesisi137 – 1371Y → A or F: Reduces activity 1000-fold. 2 Publications
    Mutagenesisi169 – 1691R → K: Reduces activity 1000-fold. 1 Publication
    Mutagenesisi169 – 1691R → M: Loss of activity. 1 Publication
    Mutagenesisi233 – 2331R → K: Reduces activity 1000-fold. 1 Publication
    Mutagenesisi233 – 2331R → M: Loss of activity. 1 Publication
    Mutagenesisi285 – 2851D → A: Reduces activity 100000-fold. 1 Publication

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 390390Isoaspartyl dipeptidasePRO_0000079178Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei162 – 1621N6-carboxylysine4 Publications

    Post-translational modificationi

    Carbamylation allows a single lysine to coordinate two zinc ions (PubMed:12718528, PubMed:12946361, PubMed:15882050, PubMed:16289685).4 Publications

    Proteomic databases

    PaxDbiP39377.
    PRIDEiP39377.

    Interactioni

    Protein-protein interaction databases

    DIPiDIP-10001N.
    IntActiP39377. 4 interactions.
    STRINGi511145.b4328.

    Structurei

    Secondary structure

    1
    390
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi5 – 73Combined sources
    Beta strandi10 – 145Combined sources
    Beta strandi16 – 2510Combined sources
    Beta strandi27 – 315Combined sources
    Beta strandi34 – 396Combined sources
    Beta strandi46 – 494Combined sources
    Beta strandi51 – 544Combined sources
    Beta strandi59 – 624Combined sources
    Beta strandi64 – 696Combined sources
    Helixi80 – 823Combined sources
    Helixi89 – 946Combined sources
    Beta strandi97 – 1026Combined sources
    Helixi113 – 12614Combined sources
    Beta strandi128 – 1358Combined sources
    Beta strandi137 – 1404Combined sources
    Beta strandi144 – 1463Combined sources
    Helixi148 – 1547Combined sources
    Beta strandi158 – 16710Combined sources
    Helixi175 – 19218Combined sources
    Beta strandi197 – 2026Combined sources
    Turni206 – 2094Combined sources
    Helixi210 – 2178Combined sources
    Helixi223 – 2253Combined sources
    Beta strandi226 – 2294Combined sources
    Helixi231 – 2333Combined sources
    Helixi235 – 24612Combined sources
    Beta strandi251 – 2544Combined sources
    Beta strandi259 – 2613Combined sources
    Helixi263 – 27210Combined sources
    Helixi277 – 2793Combined sources
    Beta strandi280 – 2834Combined sources
    Beta strandi289 – 2935Combined sources
    Beta strandi295 – 2973Combined sources
    Beta strandi299 – 3046Combined sources
    Helixi309 – 32113Combined sources
    Helixi325 – 3295Combined sources
    Helixi330 – 3323Combined sources
    Helixi334 – 3396Combined sources
    Beta strandi356 – 3594Combined sources
    Beta strandi365 – 3706Combined sources
    Beta strandi373 – 3775Combined sources
    Beta strandi380 – 3834Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1ONWX-ray1.65A/B1-390[»]
    1ONXX-ray2.10A/B1-390[»]
    1PO9X-ray2.00A/B1-390[»]
    1POJX-ray3.30A/B1-390[»]
    1POKX-ray2.70A/B1-390[»]
    1YBQX-ray2.00A/B1-390[»]
    2AQOX-ray1.95A/B1-390[»]
    2AQVX-ray1.95A/B1-390[»]
    ProteinModelPortaliP39377.
    SMRiP39377. Positions 1-389.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP39377.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni75 – 773Substrate binding

    Sequence similaritiesi

    Belongs to the peptidase M38 family.Curated

    Phylogenomic databases

    eggNOGiNOG04347.
    HOGENOMiHOG000275891.
    InParanoidiP39377.
    KOiK01305.
    OMAiPTHINRN.
    OrthoDBiEOG625JTQ.
    PhylomeDBiP39377.

    Family and domain databases

    Gene3Di2.30.40.10. 1 hit.
    InterProiIPR011059. Metal-dep_hydrolase_composite.
    IPR010229. Pept_M38_dipep.
    [Graphical view]
    PIRSFiPIRSF001238. IadA. 1 hit.
    SUPFAMiSSF51338. SSF51338. 2 hits.
    TIGRFAMsiTIGR01975. isoAsp_dipep. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    P39377-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MIDYTAAGFT LLQGAHLYAP EDRGICDVLV ANGKIIAVAS NIPSDIVPNC
    60 70 80 90 100
    TVVDLSGQIL CPGFIDQHVH LIGGGGEAGP TTRTPEVALS RLTEAGVTSV
    110 120 130 140 150
    VGLLGTDSIS RHPESLLAKT RALNEEGISA WMLTGAYHVP SRTITGSVEK
    160 170 180 190 200
    DVAIIDRVIG VKCAISDHRS AAPDVYHLAN MAAESRVGGL LGGKPGVTVF
    210 220 230 240 250
    HMGDSKKALQ PIYDLLENCD VPISKLLPTH VNRNVPLFEQ ALEFARKGGT
    260 270 280 290 300
    IDITSSIDEP VAPAEGIARA VQAGIPLARV TLSSDGNGSQ PFFDDEGNLT
    310 320 330 340 350
    HIGVAGFETL LETVQVLVKD YDFSISDALR PLTSSVAGFL NLTGKGEILP
    360 370 380 390
    GNDADLLVMT PELRIEQVYA RGKLMVKDGK ACVKGTFETA
    Length:390
    Mass (Da):41,084
    Last modified:February 1, 1995 - v1
    Checksum:i9CEEC838381545B5
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U15029 Genomic DNA. Translation: AAC43299.1.
    U14003 Genomic DNA. Translation: AAA97224.1.
    U00096 Genomic DNA. Translation: AAC77284.1.
    AP009048 Genomic DNA. Translation: BAE78321.1.
    PIRiB55889.
    RefSeqiNP_418748.1. NC_000913.3.

    Genome annotation databases

    EnsemblBacteriaiAAC77284; AAC77284; b4328.
    BAE78321; BAE78321; BAE78321.
    GeneIDi948853.
    KEGGiecj:Y75_p4214.
    eco:b4328.
    PATRICi32124258. VBIEscCol129921_4472.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U15029 Genomic DNA. Translation: AAC43299.1.
    U14003 Genomic DNA. Translation: AAA97224.1.
    U00096 Genomic DNA. Translation: AAC77284.1.
    AP009048 Genomic DNA. Translation: BAE78321.1.
    PIRiB55889.
    RefSeqiNP_418748.1. NC_000913.3.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1ONWX-ray1.65A/B1-390[»]
    1ONXX-ray2.10A/B1-390[»]
    1PO9X-ray2.00A/B1-390[»]
    1POJX-ray3.30A/B1-390[»]
    1POKX-ray2.70A/B1-390[»]
    1YBQX-ray2.00A/B1-390[»]
    2AQOX-ray1.95A/B1-390[»]
    2AQVX-ray1.95A/B1-390[»]
    ProteinModelPortaliP39377.
    SMRiP39377. Positions 1-389.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    DIPiDIP-10001N.
    IntActiP39377. 4 interactions.
    STRINGi511145.b4328.

    Protein family/group databases

    MEROPSiM38.001.

    Proteomic databases

    PaxDbiP39377.
    PRIDEiP39377.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsemblBacteriaiAAC77284; AAC77284; b4328.
    BAE78321; BAE78321; BAE78321.
    GeneIDi948853.
    KEGGiecj:Y75_p4214.
    eco:b4328.
    PATRICi32124258. VBIEscCol129921_4472.

    Organism-specific databases

    EchoBASEiEB2455.
    EcoGeneiEG12567. iadA.

    Phylogenomic databases

    eggNOGiNOG04347.
    HOGENOMiHOG000275891.
    InParanoidiP39377.
    KOiK01305.
    OMAiPTHINRN.
    OrthoDBiEOG625JTQ.
    PhylomeDBiP39377.

    Enzyme and pathway databases

    BioCyciEcoCyc:G7925-MONOMER.
    ECOL316407:JW4291-MONOMER.
    MetaCyc:G7925-MONOMER.
    BRENDAi3.4.19.5. 2026.
    SABIO-RKP39377.

    Miscellaneous databases

    EvolutionaryTraceiP39377.
    PROiP39377.

    Family and domain databases

    Gene3Di2.30.40.10. 1 hit.
    InterProiIPR011059. Metal-dep_hydrolase_composite.
    IPR010229. Pept_M38_dipep.
    [Graphical view]
    PIRSFiPIRSF001238. IadA. 1 hit.
    SUPFAMiSSF51338. SSF51338. 2 hits.
    TIGRFAMsiTIGR01975. isoAsp_dipep. 1 hit.
    ProtoNetiSearch...

    Publicationsi

    « Hide 'large scale' publications
    1. "Purification and characterization of an isoaspartyl dipeptidase from Escherichia coli."
      Gary J.D., Clarke S.
      J. Biol. Chem. 270:4076-4087(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 1-24; 35-39; 84-91; 112-118; 122-147; 170-185; 187-204; 226-238; 247-264 AND 365-371, FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE.
      Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
    2. "Analysis of the Escherichia coli genome VI: DNA sequence of the region from 92.8 through 100 minutes."
      Burland V.D., Plunkett G. III, Sofia H.J., Daniels D.L., Blattner F.R.
      Nucleic Acids Res. 23:2105-2119(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / MG1655 / ATCC 47076.
    3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / MG1655 / ATCC 47076.
    4. "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110."
      Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.
      Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
      Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
    5. "Purification and properties of a beta-aspartyl peptidase from Escherichia coli."
      Haley E.E.
      J. Biol. Chem. 243:5748-5752(1968) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, CATALYTIC ACTIVITY, ENZYME REGULATION, BIOPHYSICOCHEMICAL PROPERTIES.
    6. "High-resolution X-ray structure of isoaspartyl dipeptidase from Escherichia coli."
      Thoden J.B., Marti-Arbona R., Raushel F.M., Holden H.M.
      Biochemistry 42:4874-4882(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 13-389 IN COMPLEX WITH ASPARTATE AND ZINC IONS, FUNCTION, COFACTOR, CARBAMYLATION AT LYS-162.
    7. "X-ray structure of isoaspartyl dipeptidase from E.coli: a dinuclear zinc peptidase evolved from amidohydrolases."
      Jozic D., Kaiser J.T., Huber R., Bode W., Maskos K.
      J. Mol. Biol. 332:243-256(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) IN COMPLEX WITH INHIBITOR; ASPARAGINE AND ZINC IONS, COFACTOR, ACTIVE SITE, CARBAMYLATION AT LYS-162.
      Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
    8. "Mechanism of the reaction catalyzed by isoaspartyl dipeptidase from Escherichia coli."
      Marti-Arbona R., Fresquet V., Thoden J.B., Davis M.L., Holden H.M., Raushel F.M.
      Biochemistry 44:7115-7124(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) IN COMPLEX WITH SUBSTRATE ANALOG AND ZINC IONS, CATALYTIC ACTIVITY, FUNCTION, COFACTOR, CARBAMYLATION AT LYS-162, MUTAGENESIS OF GLU-77; TYR-137; ARG-169; ARG-233 AND ASP-285.
    9. "Functional significance of Glu-77 and Tyr-137 within the active site of isoaspartyl dipeptidase."
      Marti-Arbona R., Thoden J.B., Holden H.M., Raushel F.M.
      Bioorg. Chem. 33:448-458(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF MUTANTS GLN-77 AND PHE-137 IN COMPLEX WITH ZINC IONS, CARBAMYLATION AT LYS-162, MUTAGENESIS OF GLU-77 AND TYR-137.

    Entry informationi

    Entry nameiIADA_ECOLI
    AccessioniPrimary (citable) accession number: P39377
    Secondary accession number(s): Q2M5Y5
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1995
    Last sequence update: February 1, 1995
    Last modified: June 24, 2015
    This is version 136 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Escherichia coli
      Escherichia coli (strain K12): entries and cross-references to EcoGene
    2. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    3. Peptidase families
      Classification of peptidase families and list of entries
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.