|Gene:||hchA||Accession Numbers: G7055 (MetaCyc), b1967, ECK1963|
Synonyms: yzzC, yedU, Hsp31
Species: Escherichia coli K-12 substr. MG1655
Glyoxalase III converts methylglyoxal to D-lactate in a single glutathione (GSH)-independent step. The other known route for this conversion is the two-step GSH-dependent pathway catalyzed by glyoxalase I and II, methylglyoxal degradation I. Glyoxalase III was partially characterized by [Misra95], although the gene encoding the enzyme was not identified at that time. It was recently shown that glyoxalase III is identical to Hsp31 in E. coli [Subedi11].
Hsp31 was first identified as a chaperone that interacts with partially and fully denatured proteins [Sastry02, Malki03]. At elevated temperatures, Hsp31 homodimers bind to substrates undergoing denaturation, and upon temperature decrease the chaperone dissociates from the renatured substrates [Sastry02]. Hsp31 appears to have weak proteolytic activity using BSA as a substrate [Lee03]; others have found no endo- or exopeptidase activity [Malki03, Zhao03]. Later, Hsp31 was shown to have an aminopeptidase activity with short peptide substrates that is abolished in a C185A mutant [Malki05].
Hsp31 may bind ATP, but does not hydrolyze it [Sastry02, Malki03]. ATP induces conformational changes within Hsp31 and is inhibitory with respect to chaperone activity at high temperatures [Sastry02].
Each Hsp31 monomer comprises two domains separated by a flexible linker region [Quigley03, Quigley04]. Crystal structures are presented at 1.6 Å [Quigley03], 2.2 Å [Zhao03], 2.7 Å [Quigley04] and 2.8 Å [Lee03] resolution. Analysis of a variety of mutants identified the linker-loop region of Hsp31 as a gate which may control access of nonnative proteins to the high-affinity substrate binding site and which is thermally activated [Sastry04]. Extensions of Hsp31 with histidine tags at either its N- or C-terminus abolish chaperone activity [Sastry09].
An hchA mutant has a growth defect at 48°C and is strongly affected in its ability to recover from transient exposure to 50°C [Mujacic04]. In stationary phase, an hchA mutant is more sensitive to methylglyoxal [Subedi11] and acid stress [Mujacic07] than wild type.
Unlike glyoxalases I and II, glyoxalase III activity increases at the transition to stationary phase; the increase is dependent on RpoS [Benov04]. Glyoxalase III activity is not induced by growth in the presence of methylglyoxal [OkadoMatsumoto00]. Expression of hchA is induced by heat shock [Richmond99a]. hchA is a member of the σS stress regulon [Mujacic06], and Hsp31 expression is also induced by osmotic stress [Weber06]. The stability of the hchA transcript is higher at increased temperature [Rasouly07].
|Map Position: [2,033,859 -> 2,034,710]|
Molecular Weight of Polypeptide: 31.19 kD (from nucleotide sequence), 31 kD (experimental) [Sastry02 ]
Molecular Weight of Multimer: 62.0 kD (experimental) [Sastry02]
Unification Links: ASAP:ABE-0006529 , DIP:DIP-11851N , EchoBASE:EB1705 , EcoGene:EG11755 , EcoliWiki:b1967 , ModBase:P31658 , OU-Microarray:b1967 , PortEco:hchA , PR:PRO_000022864 , Pride:P31658 , Protein Model Portal:P31658 , RefSeq:NP_416476 , RegulonDB:G7055 , SMR:P31658 , String:511145.b1967 , UniProt:P31658
Relationship Links: InterPro:IN-FAMILY:IPR002818 , InterPro:IN-FAMILY:IPR017283 , InterPro:IN-FAMILY:IPR029062 , PDB:Structure:1IZY , PDB:Structure:1IZZ , PDB:Structure:1N57 , PDB:Structure:1ONS , PDB:Structure:1PV2 , Pfam:IN-FAMILY:PF01965
|Biological Process:||GO:0010447 - response to acidic pH
GO:0019243 - methylglyoxal catabolic process to D-lactate [Subedi11]
GO:0019249 - lactate biosynthetic process [Subedi11]
GO:0051595 - response to methylglyoxal [Subedi11]
GO:0042026 - protein refolding [GOA06, GOA et al., 2001]
|Molecular Function:||GO:0005515 - protein binding
GO:0019172 - glyoxalase III activity [Subedi11]
GO:0008270 - zinc ion binding [GOA06]
GO:0016787 - hydrolase activity [UniProt-GOA, 2011]
GO:0016829 - lyase activity [UniProt-GOA, 2011, GOA et al., 2001]
GO:0046872 - metal ion binding [UniProt-GOA, 2011]
GO:0051082 - unfolded protein binding [GOA06]
|Cellular Component:||GO:0005829 - cytosol
[Diaz-Mejia et al., 2009, Ishihama et al., 2008, Lopez-Campistrous et al., 2005, Lasserre et al., 2006]
GO:0005737 - cytoplasm [UniProt-GOA, 2011a, UniProt-GOA, 2011, GOA06]
|MultiFun Terms:||cell processes → protection → detoxification|
|information transfer → protein related → chaperoning, repair (refolding)|
Enzymatic reaction of: glyoxalase
EC Number: 184.108.40.206
The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction of enzyme catalysis.
The reaction is irreversible in the direction shown.
Inhibitors (Unknown Mechanism): Zn2+ [Subedi11] , Cu2+ [Subedi11] , p-hydroxymercuribenzoate [Misra95, Comment 1] , 5,5'-dithio-bis-2-nitrobenzoate [Misra95, Comment 1] , N-ethylmaleimide [Misra95, Comment 1]
T(opt): 35-40 °C [Subedi11]
pH(opt): 6-8 [Misra95]
|Chain||2 -> 283|
Peter D. Karp on Thu Jan 16, 2003:
Predicted gene function revised as a result of E. coli genome reannotation by Serres et al. [Serres01 ].
Markus Krummenacker on Tue Oct 14, 1997:
Gene object created from Blattner lab Genbank (v. M52) entry.
Arifuzzaman06: Arifuzzaman M, Maeda M, Itoh A, Nishikata K, Takita C, Saito R, Ara T, Nakahigashi K, Huang HC, Hirai A, Tsuzuki K, Nakamura S, Altaf-Ul-Amin M, Oshima T, Baba T, Yamamoto N, Kawamura T, Ioka-Nakamichi T, Kitagawa M, Tomita M, Kanaya S, Wada C, Mori H (2006). "Large-scale identification of protein-protein interaction of Escherichia coli K-12." Genome Res 16(5);686-91. PMID: 16606699
Diaz-Mejia et al., 2009: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114
Ishihama et al., 2008: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323
Kim02: Kim OG, Kim IK, Kim GH, Ko J, Park C, Suh PG, Kang SO, Lee HS, Cha SS (2002). "Crystallization and preliminary X-ray crystallographic analysis of a yedU gene product from Escherichia coli." Acta Crystallogr D Biol Crystallogr 58(Pt 7);1217-9. PMID: 12077448
Lasserre et al., 2006: Lasserre JP, Beyne E, Pyndiah S, Lapaillerie D, Claverol S, Bonneu M (2006). "A complexomic study of Escherichia coli using two-dimensional blue native/SDS polyacrylamide gel electrophoresis." Electrophoresis 27(16);3306-21. PMID: 16858726
Lee03: Lee SJ, Kim SJ, Kim IK, Ko J, Jeong CS, Kim GH, Park C, Kang SO, Suh PG, Lee HS, Cha SS (2003). "Crystal structures of human DJ-1 and Escherichia coli Hsp31, which share an evolutionarily conserved domain." J Biol Chem 278(45);44552-9. PMID: 12939276
Lopez-Campistrous et al., 2005: Lopez-Campistrous A, Semchuk P, Burke L, Palmer-Stone T, Brokx SJ, Broderick G, Bottorff D, Bolch S, Weiner JH, Ellison MJ (2005). "Localization, annotation, and comparison of the Escherichia coli K-12 proteome under two states of growth." Mol Cell Proteomics 4(8);1205-9. PMID: 15911532
Malki05: Malki A, Caldas T, Abdallah J, Kern R, Eckey V, Kim SJ, Cha SS, Mori H, Richarme G (2005). "Peptidase activity of the Escherichia coli Hsp31 chaperone." J Biol Chem 280(15);14420-6. PMID: 15550391
Misra95: Misra K, Banerjee AB, Ray S, Ray M (1995). "Glyoxalase III from Escherichia coli: a single novel enzyme for the conversion of methylglyoxal into D-lactate without reduced glutathione." Biochem J 1995;305 ( Pt 3);999-1003. PMID: 7848303
Mujacic04: Mujacic M, Bader MW, Baneyx F (2004). "Escherichia coli Hsp31 functions as a holding chaperone that cooperates with the DnaK-DnaJ-GrpE system in the management of protein misfolding under severe stress conditions." Mol Microbiol 51(3);849-59. PMID: 14731284
Quigley03: Quigley PM, Korotkov K, Baneyx F, Hol WG (2003). "The 1.6-A crystal structure of the class of chaperones represented by Escherichia coli Hsp31 reveals a putative catalytic triad." Proc Natl Acad Sci U S A 100(6);3137-42. PMID: 12621151
Quigley04: Quigley PM, Korotkov K, Baneyx F, Hol WG (2004). "A new native EcHsp31 structure suggests a key role of structural flexibility for chaperone function." Protein Sci 13(1);269-77. PMID: 14691241
Rajagopala14: Rajagopala SV, Sikorski P, Kumar A, Mosca R, Vlasblom J, Arnold R, Franca-Koh J, Pakala SB, Phanse S, Ceol A, Hauser R, Siszler G, Wuchty S, Emili A, Babu M, Aloy P, Pieper R, Uetz P (2014). "The binary protein-protein interaction landscape of Escherichia coli." Nat Biotechnol 32(3);285-90. PMID: 24561554
Sastry02: Sastry MS, Korotkov K, Brodsky Y, Baneyx F (2002). "Hsp31, the Escherichia coli yedU gene product, is a molecular chaperone whose activity is inhibited by ATP at high temperatures." J Biol Chem 277(48);46026-34. PMID: 12235139
Sastry04: Sastry MS, Quigley PM, Hol WG, Baneyx F (2004). "The linker-loop region of Escherichia coli chaperone Hsp31 functions as a gate that modulates high-affinity substrate binding at elevated temperatures." Proc Natl Acad Sci U S A 101(23);8587-92. PMID: 15173574
Weber06: Weber A, Kogl SA, Jung K (2006). "Time-dependent proteome alterations under osmotic stress during aerobic and anaerobic growth in Escherichia coli." J Bacteriol 188(20);7165-75. PMID: 17015655
Yoshida93: Yoshida T, Ueguchi C, Yamada H, Mizuno T (1993). "Function of the Escherichia coli nucleoid protein, H-NS: molecular analysis of a subset of proteins whose expression is enhanced in a hns deletion mutant." Mol Gen Genet 237(1-2);113-22. PMID: 8455549
Zhao03: Zhao Y, Liu D, Kaluarachchi WD, Bellamy HD, White MA, Fox RO (2003). "The crystal structure of Escherichia coli heat shock protein YedU reveals three potential catalytic active sites." Protein Sci 12(10);2303-11. PMID: 14500888
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