hchA

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

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

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

Activity 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

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 key	Position(s)	DescriptionActions	Length
Metal bindingⁱ	86	Zinc1 Publication	1
Metal bindingⁱ	91	Zinc1 Publication	1
Metal bindingⁱ	123	Zinc1 Publication	1
Active siteⁱ	185	NucleophileCurated	1

GO - Molecular functionⁱ

DNA-binding transcription factor activity Source: GO_Central
glyoxalase III activity
Source: EcoCyc
Inferred from direct assayⁱ
- 21696459
hydrolase activity Source: UniProtKB-KW
metal ion binding Source: UniProtKB-KW
protein deglycase activity
Source: EcoCyc
Inferred from direct assayⁱ
- 26102038

View the complete GO annotation on QuickGO ...

GO - Biological processⁱ

DNA repair
Source: EcoCyc
Inferred from mutant phenotypeⁱ
- 28596309
methylglyoxal catabolic process to D-lactate via S-lactoyl-glutathione
Source: EcoCyc
Inferred from mutant phenotypeⁱ
- 21696459
protein deglycosylation
Source: EcoCyc
Inferred from mutant phenotypeⁱ
- 26102038
protein repair
Source: EcoCyc
Inferred from direct assayⁱ
- 26102038
regulation of transcription, DNA-templated Source: GO_Central
response to acidic pH
Source: EcoCyc
Inferred from mutant phenotypeⁱ
- 17158627
response to methylglyoxal
Source: EcoCyc
Inferred from mutant phenotypeⁱ
- 21696459
RNA repair
Source: EcoCyc
Inferred from mutant phenotypeⁱ
- 28596309

View the complete GO annotation on QuickGO ...

Keywordsⁱ

Molecular function	Chaperone, Hydrolase, Lyase
Biological process	DNA damage, DNA repair, Stress response
Ligand	Metal-binding, Zinc

Enzyme and pathway databases

BioCycⁱ	EcoCyc:G7055-MONOMER MetaCyc:G7055-MONOMER

BioCycⁱ

EcoCyc:G7055-MONOMER
MetaCyc:G7055-MONOMER

Protein family/group databases

MoonProtⁱ	P31658

MoonProtⁱ

P31658

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
Organismⁱ	Escherichia coli (strain K12)
Taxonomic identifierⁱ	83333 [NCBI]
Taxonomic lineageⁱ	cellular organisms › Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacterales › Enterobacteriaceae › Escherichia › Escherichia coli
Proteomesⁱ	UP000000318 Componentⁱ: Chromosome UP000000625 Componentⁱ: Chromosome

Organism-specific databases

EcoGeneⁱ	EG11755 hchA

EcoGeneⁱ

EG11755 hchA

Subcellular locationⁱ

Cytoplasm

GO - Cellular componentⁱ

cytosol
Source: EcoCyc
Inferred from direct assayⁱ
- 15911532
- 18304323

View the complete GO annotation on QuickGO ...

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 key	Position(s)	DescriptionActions	Length
Mutagenesisⁱ	77	E → A: Loss of glyoxalase activity. 1 Publication	1
Mutagenesisⁱ	185	C → A: Loss of glyoxalase and aminopeptidase activities. 3 Publications	1
Mutagenesisⁱ	186	H → A: Shows approximately 17% remaining glyoxalase activity compared with that of the wild-type. 1 Publication	1

PTM / Processingⁱ

Molecule processing

Feature key	Position(s)	DescriptionActions	Graphical view	Length
Initiator methionineⁱ		Removed1 Publication
ChainⁱPRO_0000209412	2 – 283	Protein/nucleic acid deglycase 1Add BLAST		282

Proteomic databases

PaxDbⁱ	P31658
PRIDEⁱ	P31658

2D gel databases

SWISS-2DPAGEⁱ	P31658

SWISS-2DPAGEⁱ

P31658

Expressionⁱ

Inductionⁱ

By heat shock.

Interactionⁱ

Subunit structureⁱ

Homodimer.3 Publications

Binary interactionsⁱ

With	Entry	#Exp.	IntAct	Notes
asnC	P0ACI6	2	EBI-909144,EBI-1133670

With

Entry

#Exp.

IntAct

Notes

asnC

P0ACI6

2

EBI-909144,EBI-1133670

Protein-protein interaction databases

BioGridⁱ	4260394, 23 interactors
Database of interacting proteins More...DIPⁱ	DIP-11851N
IntActⁱ	P31658, 32 interactors
STRINGⁱ	316385.ECDH10B_2110

Structureⁱ

Secondary structure

Legend: HelixTurnBeta strandPDB Structure known for this area

Feature key	Position(s)	DescriptionActions	Length
Beta strandⁱ	8 – 11	Combined sources	4
Beta strandⁱ	18 – 20	Combined sources	3
Helixⁱ	23 – 29	Combined sources	7
Beta strandⁱ	50 – 54	Combined sources	5
Beta strandⁱ	60 – 62	Combined sources	3
Beta strandⁱ	68 – 70	Combined sources	3
Helixⁱ	75 – 87	Combined sources	13
Beta strandⁱ	92 – 99	Combined sources	8
Helixⁱ	106 – 108	Combined sources	3
Helixⁱ	116 – 128	Combined sources	13
Helixⁱ	133 – 138	Combined sources	6
Beta strandⁱ	145 – 151	Combined sources	7
Helixⁱ	155 – 158	Combined sources	4
Helixⁱ	161 – 163	Combined sources	3
Helixⁱ	165 – 176	Combined sources	12
Beta strandⁱ	180 – 184	Combined sources	5
Helixⁱ	187 – 194	Combined sources	8
Beta strandⁱ	195 – 197	Combined sources	3
Turnⁱ	200 – 203	Combined sources	4
Helixⁱ	211 – 215	Combined sources	5
Turnⁱ	216 – 221	Combined sources	6
Beta strandⁱ	222 – 225	Combined sources	4
Beta strandⁱ	227 – 229	Combined sources	3
Helixⁱ	231 – 237	Combined sources	7
Beta strandⁱ	251 – 254	Combined sources	4
Beta strandⁱ	257 – 262	Combined sources	6
Helixⁱ	263 – 265	Combined sources	3
Helixⁱ	266 – 281	Combined sources	16

Show more details

3D structure databases

ProteinModelPortalⁱ	P31658
SMRⁱ	P31658
ModBaseⁱ	Search...
MobiDBⁱ	Search...

Miscellaneous databases

EvolutionaryTraceⁱ	P31658

EvolutionaryTraceⁱ

P31658

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

eggNOGⁱ	ENOG4105TMR Bacteria COG0693 LUCA
HOGENOMⁱ	HOG000221774
InParanoidⁱ	P31658
KEGG Orthology (KO) More...KOⁱ	K05523
OMAⁱ	PMYHLDK

Family and domain databases

Gene3Dⁱ	3.40.50.880, 1 hit
HAMAPⁱ	MF_01046 Deglycase_HchA, 1 hit
InterProⁱ	View protein in InterPro IPR029062 Class_I_gatase-like IPR017283 HchA
PANTHERⁱ	PTHR11019:SF109 PTHR11019:SF109, 1 hit
PIRSFⁱ	PIRSF037798 Chaperone_HchA, 1 hit
SUPFAMⁱ	SSF52317 SSF52317, 1 hit

Sequenceⁱ

Sequence statusⁱ: Complete.

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

P31658-1 [UniParc]FASTA Add 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
PIRⁱ	C64961
NCBI Reference Sequences More...RefSeqⁱ	NP_416476.1, NC_000913.3 WP_000218212.1, NZ_LN832404.1

Genome annotation databases

EnsemblBacteriaⁱ	AAC75033; AAC75033; b1967 BAA15794; BAA15794; BAA15794
GeneIDⁱ	946481
KEGGⁱ	ecj:JW1950 eco:b1967
PATRICⁱ	fig\|1411691.4.peg.283

Protein	Similar proteins		Species	Score	Length	Source
P31658	Protein/nucleic acid deglycase HchA		ECOBW		283	UniRef100_C4ZQN7
Protein/nucleic acid deglycase HchA		ECODH		283
Protein/nucleic acid deglycase HchA		ECOLX		283
Protein/nucleic acid deglycase HchA		Escherichia coli MS 117-3		283
Protein/nucleic acid deglycase HchA		Escherichia coli UMNK88		283
+38

Protein	Similar proteins		Species	Score	Length	Source
P31658	Protein/nucleic acid deglycase HchA		ECO57		283	UniRef90_Q8XB78
Protein/nucleic acid deglycase HchA		ECO5E		283
Protein/nucleic acid deglycase HchA		ECOBW		283
Protein/nucleic acid deglycase HchA		ECODH		283
Protein/nucleic acid deglycase HchA		ECO24		283
+608

Protein	Similar proteins		Species	Score	Length	Source
P31658	Protein/nucleic acid deglycase HchA		ECO57		283	UniRef50_Q8XB78
Protein/nucleic acid deglycase HchA		ECO5E		283
Protein/nucleic acid deglycase HchA		ECOBW		283
Protein/nucleic acid deglycase HchA		ECODH		283
Protein/nucleic acid deglycase HchA		ECO7I		283
+711

Entry informationⁱ

Entry nameⁱ	HCHA_ECOLI
Accessionⁱ	P31658Primary (citable) accession number: P31658 Secondary accession number(s): P76338
Entry historyⁱ	Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
	Last sequence update:	January 23, 2007
	Last modified:	September 12, 2018
	This is version 154 of the entry and version 3 of the sequence. See complete history.
Entry statusⁱ	Reviewed (UniProtKB/Swiss-Prot)
Annotation program	Prokaryotic Protein Annotation Program

Miscellaneousⁱ

Keywords - Technical termⁱ

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

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UniParc

Help

UniRef

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Supporting data

UniProtKB - P31658 (HCHA_ECOLI)

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Protein/nucleic acid deglycase 1

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<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functioni

Miscellaneous

Caution

<p>This subsection of the ‘Function’ section describes biophysical and chemical properties, such as maximal absorption, kinetic parameters, pH dependence, redox potentials and temperature dependence.<p><a href='/help/biophysicochemical_properties' target='_top'>More...</a></p>Kineticsi

pH dependencei

Temperature dependencei

Sites

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

GO - Biological processi

Enzyme and pathway databases

Protein family/group databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

GO - Cellular componenti

Keywords - Cellular componenti

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

Mutagenesis

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Proteomic databases

2D gel databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

Protein-protein interaction databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

<p>This subsection of the ‘Family and domains’ section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Phylogenomic databases

Family and domain databases

Sequence databases

Genome annotation databases

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This section contains any relevant information that doesn’t fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

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Functionⁱ

Kineticsⁱ

pH dependenceⁱ

Temperature dependenceⁱ

GO - Molecular functionⁱ

GO - Biological processⁱ

Names & Taxonomyⁱ

Subcellular locationⁱ

GO - Cellular componentⁱ

Keywords - Cellular componentⁱ

Pathology & Biotechⁱ

PTM / Processingⁱ

Expressionⁱ

Interactionⁱ

Structureⁱ

Family & Domainsⁱ

Sequence similaritiesⁱ

Entry informationⁱ

Miscellaneousⁱ

Keywords - Technical termⁱ