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Protein

Protein/nucleic acid deglycase 1

Gene

hchA

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

Functioni

Protein and nucleotide deglycase that catalyzes the deglycation of the Maillard adducts formed between amino groups of proteins or nucleotides and reactive carbonyl groups of glyoxals (PubMed:26102038, PubMed:26774339, PubMed:28596309). Thus, functions as a protein deglycase that repairs methylglyoxal- and glyoxal-glycated proteins, and releases repaired proteins and lactate or glycolate, respectively. Deglycates cysteine, arginine and lysine residues in proteins, and thus reactivates these proteins by reversing glycation by glyoxals. Is able to repair glycated serum albumin, aspartate aminotransferase, glyceraldehyde-3-phosphate dehydrogenase, and fructose biphosphate aldolase. Acts on early glycation intermediates (hemithioacetals and aminocarbinols), preventing the formation of Schiff bases and advanced glycation endproducts (AGE) that cause irreversible damage (PubMed:26102038, PubMed:26774339). Also functions as a nucleotide deglycase able to repair glycated guanine in the free nucleotide pool (GTP, GDP, GMP, dGTP) and in DNA and RNA. Is thus involved in a major nucleotide repair system named guanine glycation repair (GG repair), dedicated to reversing methylglyoxal and glyoxal damage via nucleotide sanitization and direct nucleic acid repair (PubMed:28596309). Has been reported to display chaperone, peptidase and glutathione-independent glyoxalase activities (PubMed:12235139, PubMed:12565879, PubMed:14731284, PubMed:15550391, PubMed:7848303, PubMed:21696459). However, these apparently disparate activities are all recruited to execute its protein deglycase primary function (PubMed:26102038, PubMed:26774339). Plays an important role in protecting cells from carbonyl stress, severe heat shock and starvation, as well as in acid resistance of stationary-phase cells (PubMed:12235139, PubMed:16796689, PubMed:17158627).11 Publications

Miscellaneous

According to some authors, HchA exhibits an exceedingly weak proteolytic activity against bovine serum albumin (BSA) and some peptidase activity against small single amino acids conjugated to a fluorogenic reporter (PubMed:12939276). Another report showed that HchA does not display any significant proteolytic activity but displays a physiologically relevant aminopeptidase activity (PubMed:15550391).2 Publications

Catalytic activityi

(R)-lactate = methylglyoxal + H2O.2 Publications
An N(omega)-(1-hydroxy-2-oxopropyl)-[protein]-L-arginine + H2O = a [protein]-L-arginine + (R)-lactate.2 Publications
An N6-(1-hydroxy-2-oxopropyl)-[protein]-L-lysine + H2O = a [protein]-L-lysine + (R)-lactate.2 Publications
An S-(1-hydroxy-2-oxopropyl)-[protein]-L-cysteine + H2O = a [protein]-L-cysteine + (R)-lactate.2 Publications

Enzyme regulationi

The glyoxalase activity is inhibited by copper and zinc cations, activated by ferrous cations, and inactivated by thiol-blocking reagents (PubMed:21696459, PubMed:7848303). The aminopeptidase activity is inhibited by iodoacetamide, dithiothreitol, EDTA and 1, 10-phenanthroline (PubMed:15550391). Binding of ATP at high temperatures induces a conformational change that reduces HchA surface hydrophobicity, interferes with its ability to capture substrate proteins and inhibits chaperone activity (PubMed:12235139).4 Publications

Kineticsi

kcat is 156.9 min(-1) for glyoxalase activity with methylglyoxal as substrate (PubMed:21696459). kcat is 0.43 min(-1) for aminopeptidase activity with Lys-AMC as substrate. kcat is 0.51 min(-1) for aminopeptidase activity with Arg-AMC as substrate. kcat is 1.1 min(-1) for aminopeptidase activity with Ala-AMC as substrate (PubMed:15550391).2 Publications
  1. KM=55 µM for Lys-AMC (at 37 degrees Celsius and pH 8.5)1 Publication
  2. KM=95 µM for Arg-AMC (at 37 degrees Celsius and pH 8.5)1 Publication
  3. KM=120 µM for Ala-AMC (at 37 degrees Celsius and pH 8.5)1 Publication
  4. KM=1.43 mM for methylglyoxal1 Publication

    pH dependencei

    Optimum pH is between 6 and 8 for glyoxalase activity (PubMed:21696459, PubMed:7848303). Significant inhibition of glyoxalase activity below pH 5 (PubMed:21696459). Optimum pH is 8 for aminopeptidase activity (PubMed:15550391).3 Publications

    Temperature dependencei

    Optimum temperature for glyoxalase activity is around 37 degrees Celsius (PubMed:21696459). Optimum temperature for aminopeptidase activity is around 43 degrees Celsius (PubMed:15550391).2 Publications

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi86Zinc1 Publication1
    Metal bindingi91Zinc1 Publication1
    Metal bindingi123Zinc1 Publication1
    Active sitei185NucleophileCurated1

    GO - Molecular functioni

    • glyoxalase III activity Source: EcoCyc
    • hydrolase activity Source: UniProtKB-KW
    • metal ion binding Source: UniProtKB-KW
    • protein deglycase activity Source: EcoCyc
    • transcription factor activity, sequence-specific DNA binding Source: GO_Central

    GO - Biological processi

    • DNA repair Source: UniProtKB-KW
    • methylglyoxal catabolic process to D-lactate via S-lactoyl-glutathione Source: EcoCyc
    • protein deglycosylation Source: EcoCyc
    • protein repair Source: EcoCyc
    • regulation of transcription, DNA-templated Source: GO_Central
    • response to acidic pH Source: EcoCyc
    • response to methylglyoxal Source: EcoCyc

    Keywordsi

    Molecular functionChaperone, Hydrolase, Lyase
    Biological processDNA damage, DNA repair, Stress response
    LigandMetal-binding, Zinc

    Enzyme and pathway databases

    BioCyciEcoCyc:G7055-MONOMER.
    MetaCyc:G7055-MONOMER.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Protein/nucleic acid deglycase 12 Publications (EC:3.1.2.-2 Publications, EC:3.5.1.-1 Publication, EC:3.5.1.1242 Publications)
    Alternative name(s):
    Glyoxalase III2 Publications (EC:4.2.1.1302 Publications)
    Holding molecular chaperone1 Publication
    Hsp311 Publication
    Maillard deglycase1 Publication
    Gene namesi
    Name:hchA
    Synonyms:yedU, yzzC
    Ordered Locus Names:b1967, JW1950
    OrganismiEscherichia coli (strain K12)
    Taxonomic identifieri83333 [NCBI]
    Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeEscherichia
    Proteomesi
    • UP000000318 Componenti: Chromosome
    • UP000000625 Componenti: Chromosome

    Organism-specific databases

    EcoGeneiEG11755. hchA.

    Subcellular locationi

    P31658:

    GO - Cellular componenti

    • cytosol Source: UniProtKB

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Disruption phenotypei

    Cells lacking this gene show a loss of glyoxalase and reduction in aminopeptidase activity (PubMed:15550391, PubMed:21696459). They accumulate methylglyoxal and are more susceptible to methylglyoxal than the parent strain (PubMed:21696459). Cells exhibit growth defects above 48 degrees Celsius and accumulate higher levels of peptides than wild-type (PubMed:14731284, PubMed:15550391). They display increased protein and DNA/RNA glycation levels, and exhibit strong mutator phenotypes (PubMed:26102038, PubMed:28596309). Moreover, the double and triple mutants lacking yhbO and yajL, and yhbO, yajL and hchA, respectively, display impressive amounts of glycated proteins, suggesting that the YhbO, YajL and Hsp31 deglycases display relatively redundant functions (PubMed:26774339). The triple mutant displays higher glycation levels of free nucleotides (GTP and dGTP) than the parental strain, and shows higher glycation levels of DNA and RNA than those of single mutants (PubMed:28596309). The hchA mutant cells show decreased viability in methylglyoxal- or glucose-containing media (PubMed:26774339).6 Publications

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi77E → A: Loss of glyoxalase activity. 1 Publication1
    Mutagenesisi185C → A: Loss of glyoxalase and aminopeptidase activities. 3 Publications1
    Mutagenesisi186H → A: Shows approximately 17% remaining glyoxalase activity compared with that of the wild-type. 1 Publication1

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Initiator methionineiRemoved1 Publication
    ChainiPRO_00002094122 – 283Protein/nucleic acid deglycase 1Add BLAST282

    Proteomic databases

    PaxDbiP31658.
    PRIDEiP31658.

    2D gel databases

    SWISS-2DPAGEiP31658.

    Expressioni

    Inductioni

    By heat shock.

    Interactioni

    Subunit structurei

    Homodimer.3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    asnCP0ACI62EBI-909144,EBI-1133670

    Protein-protein interaction databases

    BioGridi4260394. 20 interactors.
    DIPiDIP-11851N.
    IntActiP31658. 32 interactors.
    STRINGi316385.ECDH10B_2110.

    Structurei

    Secondary structure

    1283
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi8 – 11Combined sources4
    Beta strandi18 – 20Combined sources3
    Helixi23 – 29Combined sources7
    Beta strandi50 – 54Combined sources5
    Beta strandi60 – 62Combined sources3
    Beta strandi68 – 70Combined sources3
    Helixi75 – 87Combined sources13
    Beta strandi92 – 99Combined sources8
    Helixi106 – 108Combined sources3
    Helixi116 – 128Combined sources13
    Helixi133 – 138Combined sources6
    Beta strandi145 – 151Combined sources7
    Helixi155 – 158Combined sources4
    Helixi161 – 163Combined sources3
    Helixi165 – 176Combined sources12
    Beta strandi180 – 184Combined sources5
    Helixi187 – 194Combined sources8
    Beta strandi195 – 197Combined sources3
    Turni200 – 203Combined sources4
    Helixi211 – 215Combined sources5
    Turni216 – 221Combined sources6
    Beta strandi222 – 225Combined sources4
    Beta strandi227 – 229Combined sources3
    Helixi231 – 237Combined sources7
    Beta strandi251 – 254Combined sources4
    Beta strandi257 – 262Combined sources6
    Helixi263 – 265Combined sources3
    Helixi266 – 281Combined sources16

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1IZYX-ray2.80A/B1-283[»]
    1IZZX-ray2.31A1-283[»]
    1N57X-ray1.60A1-283[»]
    1ONSX-ray2.20A2-283[»]
    1PV2X-ray2.71A/B/C/D/E/F/G/H1-283[»]
    ProteinModelPortaliP31658.
    SMRiP31658.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP31658.

    Family & Domainsi

    Domaini

    Consists of a large A domain and a smaller P domain connected by a linker. The thermally induced motion of the flexible linker-loop region leads to the uncovering of a high-affinity substrate-binding site that is essential to capture nonnative proteins at high temperatures.1 Publication

    Sequence similaritiesi

    Belongs to the peptidase C56 family. HchA subfamily.UniRule annotation

    Phylogenomic databases

    eggNOGiENOG4105TMR. Bacteria.
    COG0693. LUCA.
    HOGENOMiHOG000221774.
    InParanoidiP31658.
    KOiK05523.

    Family and domain databases

    Gene3Di3.40.50.880. 1 hit.
    HAMAPiMF_01046. Deglycase_HchA. 1 hit.
    InterProiView protein in InterPro
    IPR029062. Class_I_gatase-like.
    IPR017283. HchA.
    PANTHERiPTHR11019:SF109. PTHR11019:SF109. 1 hit.
    PIRSFiPIRSF037798. Chaperone_HchA. 1 hit.
    SUPFAMiSSF52317. SSF52317. 1 hit.

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P31658-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MTVQTSKNPQ VDIAEDNAFF PSEYSLSQYT SPVSDLDGVD YPKPYRGKHK
    60 70 80 90 100
    ILVIAADERY LPTDNGKLFS TGNHPIETLL PLYHLHAAGF EFEVATISGL
    110 120 130 140 150
    MTKFEYWAMP HKDEKVMPFF EQHKSLFRNP KKLADVVASL NADSEYAAIF
    160 170 180 190 200
    VPGGHGALIG LPESQDVAAA LQWAIKNDRF VISLCHGPAA FLALRHGDNP
    210 220 230 240 250
    LNGYSICAFP DAADKQTPEI GYMPGHLTWY FGEELKKMGM NIINDDITGR
    260 270 280
    VHKDRKLLTG DSPFAANALG KLAAQEMLAA YAG
    Length:283
    Mass (Da):31,190
    Last modified:January 23, 2007 - v3
    Checksum:i5CA8A53843A83B72
    GO

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U00096 Genomic DNA. Translation: AAC75033.1.
    AP009048 Genomic DNA. Translation: BAA15794.1.
    PIRiC64961.
    RefSeqiNP_416476.1. NC_000913.3.
    WP_000218212.1. NZ_LN832404.1.

    Genome annotation databases

    EnsemblBacteriaiAAC75033; AAC75033; b1967.
    BAA15794; BAA15794; BAA15794.
    GeneIDi946481.
    KEGGiecj:JW1950.
    eco:b1967.
    PATRICifig|1411691.4.peg.283.

    Similar proteinsi

    Entry informationi

    Entry nameiHCHA_ECOLI
    AccessioniPrimary (citable) accession number: P31658
    Secondary accession number(s): P76338
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1993
    Last sequence update: January 23, 2007
    Last modified: October 25, 2017
    This is version 148 of the entry and version 3 of the sequence. See complete history.
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programProkaryotic Protein Annotation Program

    Miscellaneousi

    Caution

    The protein deglycation activity has been ascribed to a TRIS buffer artifact by a publication (PubMed:27903648), which has then been rebutted by clear biochemical experiments showing that DJ-1 family deglycases are bona fide deglycases (PubMed:28013050). Deglycase activity is even strengthened by a novel article that reports nucleotide deglycation activity (PubMed:28596309).Curated

    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