Escherichia coli K-12 substr. MG1655 Enzyme: peptidase D

Gene: pepD Accession Numbers: EG10695 (EcoCyc), b0237, ECK0238

Synonyms: pepH, carnosinase

Regulation Summary Diagram: ?

Regulation summary diagram for pepD

Subunit composition of peptidase D = [PepD]2
         peptidase D = PepD

Peptidase D (PepD) is a dipeptidase capable of breaking down a number of dipeptides with unblocked N termini [Miller78a, Schroeder94], including cysteinylglycine, a breakdown product of glutathione [Suzuki01a]. Neither proline nor non-protein amino acids are accepted in the C-terminal position [Schroeder94].

Transcription of pepD increases five fold during phosphate starvation [Henrich92]. Overexpression of pepD negatively affects biofilm formation [Brombacher03].

Citations: [Henrich89, Henrich91, Bartlow12]

Gene Citations: [Henrich90]

Locations: cytosol

Map Position: [254,259 <- 255,716] (5.48 centisomes, 20°)
Length: 1458 bp / 485 aa

Molecular Weight of Polypeptide: 52.915 kD (from nucleotide sequence), 52.0 kD (experimental) [Klein86 ]

Molecular Weight of Multimer: 100.0 kD (experimental) [Klein86]

pI: 4.7 [Schroeder94]

Unification Links: ASAP:ABE-0000809 , CGSC:415 , DIP:DIP-10456N , EchoBASE:EB0689 , EcoGene:EG10695 , EcoliWiki:b0237 , Mint:MINT-1252343 , ModBase:P15288 , OU-Microarray:b0237 , PortEco:pepD , PR:PRO_000023509 , Pride:P15288 , Protein Model Portal:P15288 , RefSeq:NP_414772 , RegulonDB:EG10695 , SMR:P15288 , String:511145.b0237 , UniProt:P15288

Relationship Links: InterPro:IN-FAMILY:IPR001160 , InterPro:IN-FAMILY:IPR002933 , InterPro:IN-FAMILY:IPR011650 , Pfam:IN-FAMILY:PF01546 , Pfam:IN-FAMILY:PF07687 , Prints:IN-FAMILY:PR00934

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Genetic Regulation Schematic: ?

Genetic regulation schematic for pepD

GO Terms:

Biological Process: GO:0043171 - peptide catabolic process Inferred from experiment [Miller78a]
GO:0006508 - proteolysis Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0008152 - metabolic process Inferred by computational analysis [GOA01a]
Molecular Function: GO:0008270 - zinc ion binding Inferred from experiment [Sevcenco11]
GO:0016805 - dipeptidase activity Inferred from experiment Inferred by computational analysis [UniProtGOA11a, Miller78a]
GO:0042803 - protein homodimerization activity Inferred from experiment [Klein86]
GO:0070573 - metallodipeptidase activity Inferred from experiment [Schroeder94]
GO:0008233 - peptidase activity Inferred by computational analysis [UniProtGOA11a]
GO:0008237 - metallopeptidase activity Inferred by computational analysis [UniProtGOA11a]
GO:0016787 - hydrolase activity Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005829 - cytosol Inferred from experiment Inferred by computational analysis [DiazMejia09, Ishihama08, LopezCampistrou05]

MultiFun Terms: information transfer protein related turnover, degradation
metabolism degradation of macromolecules proteins/peptides/glycopeptides

Essentiality data for pepD knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]
Yes [Feist07, Comment 4]

Last-Curated ? 06-Nov-2012 by Keseler I , SRI International

Enzymatic reaction of: alanylglutamate dipeptidase (peptidase D)

EC Number:

L-alanyl-L-glutamate + H2O <=> L-alanine + L-glutamate

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.

In Pathways: muropeptide degradation

Imported from MetaCyc 15-Oct-2013 by Caspi R , SRI International

Enzymatic reaction of: nonspecific dipeptidase (peptidase D)

EC Number:

a dipeptide + H2O <=> 2 a standard α amino acid

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.

Alternative Substrates for a dipeptide: carnosine [Klein86 ]

Activators (Unknown Mechanism): Co2+ [Schroeder94] , Zn2+ [Schroeder94]

T(opt): 37 °C [Schroeder94]

pH(opt): 9 [Schroeder94]

Enzymatic reaction of: cysteinylglycine dipeptidase (peptidase D)

EC Number:

L-cysteinyl-glycine + H2O <=> L-cysteine + glycine

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

The reaction is physiologically favored in the direction shown.

Sequence Features

Protein sequence of peptidase D with features indicated

Feature Class Location Citations Comment
Cleavage-of-Initial-Methionine 1
[Henrich89, UniProt11]
UniProt: Removed.
Chain 2 -> 485
UniProt: Aminoacyl-histidine dipeptidase;
Metal-Binding-Site 76
UniProt: Zinc 2; Non-Experimental Qualifier: by similarity;
Active-Site 78
UniProt: Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 115
UniProt: Zinc 1; Non-Experimental Qualifier: by similarity;
Active-Site 145
UniProt: Proton acceptor; Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 146
UniProt: Zinc 1; Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 169
UniProt: Zinc 2; Non-Experimental Qualifier: by similarity;
N6-acetyllysine-Modification 296
[Zhang09, UniProt15]
UniProt: N6-acetyllysine.
Acetylation-Modification 389
Metal-Binding-Site 457
UniProt: Zinc 1; Non-Experimental Qualifier: by similarity;

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Units:

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram


10/20/97 Gene b0237 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10695; confirmed by SwissProt match.


Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Bartlow12: Bartlow P, Tiwari N, Beitle RR, Ataai MM (2012). "Evaluation of Escherichia coli proteins that burden nonaffinity-based chromatography as a potential strategy for improved purification performance." Biotechnol Prog 28(1);137-45. PMID: 21905274

Brombacher03: Brombacher E, Dorel C, Zehnder AJ, Landini P (2003). "The curli biosynthesis regulator CsgD co-ordinates the expression of both positive and negative determinants for biofilm formation in Escherichia coli." Microbiology 149(Pt 10);2847-57. PMID: 14523117

DiazMejia09: 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

Feist07: Feist AM, Henry CS, Reed JL, Krummenacker M, Joyce AR, Karp PD, Broadbelt LJ, Hatzimanikatis V, Palsson BO (2007). "A genome-scale metabolic reconstruction for Escherichia coli K-12 MG1655 that accounts for 1260 ORFs and thermodynamic information." Mol Syst Biol 3;121. PMID: 17593909

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Henrich89: Henrich B, Schroeder U, Frank RW, Plapp R (1989). "Accurate mapping of the Escherichia coli pepD gene by sequence analysis of its 5' flanking region." Mol Gen Genet 215(3);369-73. PMID: 2651887

Henrich90: Henrich B, Monnerjahn U, Plapp R (1990). "Peptidase D gene (pepD) of Escherichia coli K-12: nucleotide sequence, transcript mapping, and comparison with other peptidase genes." J Bacteriol 1990;172(8);4641-51. PMID: 1695895

Henrich91: Henrich B, Plapp R (1991). "Locations of the genes from pepD through proA on the physical map of the Escherichia coli chromosome." J Bacteriol 173(23);7407-8. PMID: 1938933

Henrich92: Henrich B, Backes H, Klein JR, Plapp R (1992). "The promoter region of the Escherichia coli pepD gene: deletion analysis and control by phosphate concentration." Mol Gen Genet 232(1);117-25. PMID: 1313142

Ishihama08: 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

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Klein86: Klein J, Henrich B, Plapp R (1986). "Cloning and expression of the pepD gene of Escherichia coli." J Gen Microbiol 132(8);2337-43. PMID: 3540199

LopezCampistrou05: 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

Miller78a: Miller CG, Schwartz G (1978). "Peptidase-deficient mutants of Escherichia coli." J Bacteriol 135(2);603-11. PMID: 355237

Schroeder94: Schroeder U, Henrich B, Fink J, Plapp R (1994). "Peptidase D of Escherichia coli K-12, a metallopeptidase of low substrate specificity." FEMS Microbiol Lett 123(1-2);153-9. PMID: 7988883

Sevcenco11: Sevcenco AM, Pinkse MW, Wolterbeek HT, Verhaert PD, Hagen WR, Hagedoorn PL (2011). "Exploring the microbial metalloproteome using MIRAGE." Metallomics 3(12);1324-30. PMID: 22094925

Suzuki01a: Suzuki H, Kamatani S, Kim ES, Kumagai H (2001). "Aminopeptidases A, B, and N and dipeptidase D are the four cysteinylglycinases of Escherichia coli K-12." J Bacteriol 183(4);1489-90. PMID: 11157967

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt11: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

UniProt15: UniProt Consortium (2015). "UniProt version 2015-01 released on 2015-01-16 00:00:00." Database.

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Yu08: Yu BJ, Kim JA, Moon JH, Ryu SE, Pan JG (2008). "The diversity of lysine-acetylated proteins in Escherichia coli." J Microbiol Biotechnol 18(9);1529-36. PMID: 18852508

Zhang09: Zhang J, Sprung R, Pei J, Tan X, Kim S, Zhu H, Liu CF, Grishin NV, Zhao Y (2009). "Lysine acetylation is a highly abundant and evolutionarily conserved modification in Escherichia coli." Mol Cell Proteomics 8(2);215-25. PMID: 18723842

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
Page generated by SRI International Pathway Tools version 19.0 on Tue Oct 6, 2015, biocyc14.