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MetaCyc Enzyme: penicillin-binding protein 7

Gene: pbpG Accession Numbers: EG12015 (MetaCyc), b2134, ECK2127

Synonyms: yohB, PBP7, PBP8

Species: Escherichia coli K-12 substr. MG1655

Summary:
PBP7 is a DD-endopeptidase and is a member of the family of penicillin-binding proteins. It is involved as a auxiliary factor in maintaining the rod shape of the murein sacculus. PBP7 acts by hydrolysing D-alanyl-DAP amide bonds within murein crosslinks.

PPB7 is a soluble, periplasmic protein that is loosely membrane associated [Henderson95, Barbas86]. PBP7 has consensus motifs putting it in the family of penicillin-binding endopeptidases, as well as a signal-sequence cleavage site where its amino-terminus is clipped and a site near the carboxy-terminus where OmpT cleaves it to yield the derivative protein PBP8 [Henderson95]. This latter cleavage is a preparation artifact, as it only occurs following cell lysis or freeze-thaw perturbation of membranes [Henderson94a].

Both PBP7 and its cleavage derivative, PBP8 have D-alanyl-DAP endopeptidase activity capable of cleaving the bonds in murein sacculi but not in dimeric muropeptides [Romeis94a]. PBP7 also has minor LD-endopeptidase activity allowing it to hydrolyze some DAP-DAP murein crosslinks [Romeis94a]. A pbpG deletion mutant has no obvious growth defects [Hara96b, Henderson95]. Overexpression of pbpG also had no effect on growth [Henderson95]. dacA pbpG double mutants have an increased percentage of pentapeptides, increased numbers of crosslinkages, decreased attachment of peptidoglycan to Lpp, and an increased rate of abnormal cell morphology which was exacerbated by further deletion of dacB [Meberg04], dacC, or ampC [Nelson01a, Varma07]. A ftsZ84 dacA pbpG mutant has an increased branching phenotype [Varma04]. ftsZ84 dacA pbpG or ftsZ84 dacB pbpG mutants lyse at the nonpermissive temperature [Varma04]. Inhibition of FtsZ by SulA in a dacA pbpG mutant results in growth of spiral-shaped cells [Varma04]. Further inhibition of MreB or PBP2 in FtsZ-inhibited dacA pbpG mutants results in lemon shaped cells with polar, tubular extensions [Varma07]. Deletion of pbpG in combination with other endopeptidases and amiC results in increased chaining due to deficient septum cleavage during cell division [Priyadarshini06]. pbpG acts as a multicopy suppressor of spr thermosensitivity, which is dependent on the active site serine of PBP7 [Hara96b]. PBP8 levels are increased in minicells [Obermann94].

PBP7 binds a number of antibiotics capable of lysing non-growing cells [Tuomanen87]. PBP7 binds soluble lytic murein transglycosylase, stimulating its enzymatic activity via direct interaction and stabilizing it in vitro> [Romeis94].

Citations: [Denome99, Henderson97, Leidenix89, Fischer89a, Jacoby88, Satta95]

Locations: periplasmic space

Map Position: [2,221,960 <- 2,222,892]

Molecular Weight of Polypeptide: 33.887 kD (from nucleotide sequence), 32.0 kD (experimental) [Spratt77 ]

Unification Links: ASAP:ABE-0007050 , CGSC:36349 , DIP:DIP-48108N , EchoBASE:EB1952 , EcoGene:EG12015 , EcoliWiki:b2134 , ModBase:P0AFI5 , OU-Microarray:b2134 , PortEco:pbpG , PR:PRO_000023497 , Protein Model Portal:P0AFI5 , RefSeq:NP_416638 , RegulonDB:EG12015 , SMR:P0AFI5 , String:511145.b2134 , UniProt:P0AFI5

Relationship Links: InterPro:IN-FAMILY:IPR001967 , InterPro:IN-FAMILY:IPR012338 , InterPro:IN-FAMILY:IPR018044 , Pfam:IN-FAMILY:PF00768 , Prints:IN-FAMILY:PR00725

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0000270 - peptidoglycan metabolic process Inferred from experiment [Romeis94a]
GO:0042493 - response to drug Inferred from experiment [Tuomanen87]
GO:0043093 - FtsZ-dependent cytokinesis Inferred from experiment [Priyadarshini06]
GO:0071555 - cell wall organization Inferred from experiment Inferred by computational analysis [UniProt-GOA, 2011, Romeis94a]
GO:0006508 - proteolysis Inferred by computational analysis [GOA et al., 2001]
GO:0008360 - regulation of cell shape Inferred by computational analysis [UniProt-GOA, 2011]
GO:0009252 - peptidoglycan biosynthetic process Inferred by computational analysis [UniProt-GOA, 2011]
Molecular Function: GO:0004175 - endopeptidase activity Inferred from experiment [Romeis94a]
GO:0009002 - serine-type D-Ala-D-Ala carboxypeptidase activity Inferred by computational analysis [GOA et al., 2001]
GO:0016787 - hydrolase activity Inferred by computational analysis [UniProt-GOA, 2011]
Cellular Component: GO:0030288 - outer membrane-bounded periplasmic space Inferred by computational analysis [Diaz-Mejia et al., 2009, Romeis94a]
GO:0042597 - periplasmic space Inferred by computational analysis [UniProtGOA11, UniProt-GOA, 2011]

MultiFun Terms: cell processes cell division
cell processes protection drug resistance/sensitivity
cell structure murein
metabolism biosynthesis of macromolecules (cellular constituents) murein (peptidoglycan)

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International


Enzymatic reaction of: DD-endopeptidase (penicillin-binding protein 7)

EC Number: 3.4.-.-

peptidoglycan D-alanyl-DAP crosslink[periplasmic space] + H2O[periplasmic space] <=> peptidoglycan tetrapeptide, glycan chain 1[periplasmic space] + peptidoglycan tetrapeptide, glycan chain 2[periplasmic space]

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 peptidoglycan D-alanyl-DAP crosslink: peptidoglycan DAP-DAP crosslink [Romeis94a ]

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Inhibitors (Unknown Mechanism): bolton and Hunter derivative of ampicillin [Romeis94a] , penem CGP31608 [Romeis94a] , sodium chloride [Romeis94a] , penicillin G [Romeis94a]

T(opt): 43 °C [Romeis94a]

pH(opt): 6.2 [Romeis94a]


Sequence Features

Feature Class Location Common Name Citations Comment
Signal-Sequence 1 -> 25  
[Henderson95, UniProt11]
.
Signal-Sequence 1 -> 28 PBP7 signal sequence
[Henderson95]
 
Chain 26 -> 310  
[UniProt, 2009]
UniProt: D-alanyl-D-alanine endopeptidase;
Active-Site 67  
[UniProt10]
UniProt: Acyl-ester intermediate; Non-Experimental Qualifier: by similarity;
Active-Site 70  
[UniProt10]
UniProt: Proton acceptor; Non-Experimental Qualifier: by similarity;
Active-Site 124  
[UniProt10]
UniProt: Non-Experimental Qualifier: by similarity;
Amino-Acid-Sites-That-Bind 231  
[UniProt10]
UniProt: Substrate; Non-Experimental Qualifier: by similarity;

History:
Peter D. Karp on Wed Jan 18, 2006:
Gene right-end position adjusted based on analysis performed in the 2005 E. coli annotation update [Riley06 ].
10/20/97 Gene b2134 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG12015; confirmed by SwissProt match.


References

Barbas86: Barbas JA, Diaz J, Rodriguez-Tebar A, Vazquez D (1986). "Specific location of penicillin-binding proteins within the cell envelope of Escherichia coli." J Bacteriol 165(1);269-75. PMID: 3510188

Denome99: Denome SA, Elf PK, Henderson TA, Nelson DE, Young KD (1999). "Escherichia coli mutants lacking all possible combinations of eight penicillin binding proteins: viability, characteristics, and implications for peptidoglycan synthesis." J Bacteriol 181(13);3981-93. PMID: 10383966

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

Fischer89a: Fischer E (1989). "Osmolability of Escherichia coli and modification of [125I]ampicillin-binding by competence induction for uptake of transforming DNA." Arch Microbiol 153(1);43-6. PMID: 2692534

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

Hara96b: Hara H, Abe N, Nakakouji M, Nishimura Y, Horiuchi K (1996). "Overproduction of penicillin-binding protein 7 suppresses thermosensitive growth defect at low osmolarity due to an spr mutation of Escherichia coli." Microb Drug Resist 2(1);63-72. PMID: 9158724

Henderson94a: Henderson TA, Dombrosky PM, Young KD (1994). "Artifactual processing of penicillin-binding proteins 7 and 1b by the OmpT protease of Escherichia coli." J Bacteriol 176(1);256-9. PMID: 8282705

Henderson95: Henderson TA, Templin M, Young KD (1995). "Identification and cloning of the gene encoding penicillin-binding protein 7 of Escherichia coli." J Bacteriol 177(8);2074-9. PMID: 7721700

Henderson97: Henderson TA, Young KD, Denome SA, Elf PK (1997). "AmpC and AmpH, proteins related to the class C beta-lactamases, bind penicillin and contribute to the normal morphology of Escherichia coli." J Bacteriol 179(19);6112-21. PMID: 9324260

Jacoby88: Jacoby GH, Young KD (1988). "Unequal distribution of penicillin-binding proteins among inner membrane vesicles of Escherichia coli." J Bacteriol 170(8);3660-7. PMID: 3042758

Leidenix89: Leidenix MJ, Jacoby GH, Henderson TA, Young KD (1989). "Separation of Escherichia coli penicillin-binding proteins into different membrane vesicles by agarose electrophoresis and sizing chromatography." J Bacteriol 171(10);5680-6. PMID: 2676988

Meberg04: Meberg BM, Paulson AL, Priyadarshini R, Young KD (2004). "Endopeptidase penicillin-binding proteins 4 and 7 play auxiliary roles in determining uniform morphology of Escherichia coli." J Bacteriol 186(24);8326-36. PMID: 15576782

Nelson01a: Nelson DE, Young KD (2001). "Contributions of PBP 5 and DD-carboxypeptidase penicillin binding proteins to maintenance of cell shape in Escherichia coli." J Bacteriol 183(10);3055-64. PMID: 11325933

Obermann94: Obermann W, Holtje JV (1994). "Alterations of murein structure and of penicillin-binding proteins in minicells from Escherichia coli." Microbiology 140 ( Pt 1);79-87. PMID: 8162193

Priyadarshini06: Priyadarshini R, Popham DL, Young KD (2006). "Daughter cell separation by penicillin-binding proteins and peptidoglycan amidases in Escherichia coli." J Bacteriol 188(15);5345-55. PMID: 16855223

Riley06: Riley M, Abe T, Arnaud MB, Berlyn MK, Blattner FR, Chaudhuri RR, Glasner JD, Horiuchi T, Keseler IM, Kosuge T, Mori H, Perna NT, Plunkett G, Rudd KE, Serres MH, Thomas GH, Thomson NR, Wishart D, Wanner BL (2006). "Escherichia coli K-12: a cooperatively developed annotation snapshot--2005." Nucleic Acids Res 34(1);1-9. PMID: 16397293

Romeis94: Romeis T, Holtje JV (1994). "Specific interaction of penicillin-binding proteins 3 and 7/8 with soluble lytic transglycosylase in Escherichia coli." J Biol Chem 269(34);21603-7. PMID: 8063800

Romeis94a: Romeis T, Holtje JV (1994). "Penicillin-binding protein 7/8 of Escherichia coli is a DD-endopeptidase." Eur J Biochem 224(2);597-604. PMID: 7925376

Satta95: Satta G, Cornaglia G, Mazzariol A, Golini G, Valisena S, Fontana R (1995). "Target for bacteriostatic and bactericidal activities of beta-lactam antibiotics against Escherichia coli resides in different penicillin-binding proteins." Antimicrob Agents Chemother 39(4);812-8. PMID: 7785976

Spratt77: Spratt BG (1977). "Properties of the penicillin-binding proteins of Escherichia coli K12,." Eur J Biochem 72(2);341-52. PMID: 319999

Tuomanen87: Tuomanen E, Schwartz J (1987). "Penicillin-binding protein 7 and its relationship to lysis of nongrowing Escherichia coli." J Bacteriol 169(11);4912-5. PMID: 3312163

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

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

UniProt10: 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.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

Varma04: Varma A, Young KD (2004). "FtsZ collaborates with penicillin binding proteins to generate bacterial cell shape in Escherichia coli." J Bacteriol 186(20);6768-74. PMID: 15466028

Varma07: Varma A, de Pedro MA, Young KD (2007). "FtsZ directs a second mode of peptidoglycan synthesis in Escherichia coli." J Bacteriol 189(15);5692-704. PMID: 17513471


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Thu Dec 18, 2014, biocyc11.