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Escherichia coli K-12 substr. MG1655 Enzyme: D-alanyl-D-alanine carboxypeptidase, fraction A; penicillin-binding protein 5



Gene: dacA Accession Numbers: EG10201 (EcoCyc), b0632, ECK0625

Synonyms: pfv, PBP5

Regulation Summary Diagram: ?

Summary:
D-alanyl-D-alanine carboxypeptidase IA (PBP5) is a penicillin-sensitive, membrane-bound enzyme required for trimming the carboxy-terminal D-alanyl residues from peptidoglycan pentapeptides. β-lactam antibiotics act by binding covalently to PBPs resulting in their deactivation and ultimately leading to cell death.

The crystal structures of PBP5, PBP5 mutants, and PBP5 in complexes with substrates and substrate-like compounds have been determined [Nicholas03, Nicola05, Davies01, Nicola05a, Sauvage08].

The carboxy-terminal eighteen residues of PBP5 are sufficient to anchor a heterofusion protein to the inner membrane, whereas the signal sequence is dispensable for PBP5 localization [Jackson88]. PBP5 anchors to the inner membrane even in the absence of anionic phospholipids [Harris95]. Surface pressure tests reveal that the PBP5-membrane interaction is mostly hydrophobic in character [Harris98]. Membrane anchoring depends on the alpha-helical conformation of the eighteen residues at the carboxy-terminus [Siligardi97, Harris98]. This section of the protein appears to be deeply imbedded in various test membranes, which may suggest oblique orientation within the inner membrane in vivo [Harris02a, Harris97a]. Though PBP5 becomes urea-extractable in the presence of benzyl penicillin, indicating a role for the non-membrane domain of the protein in membrane anchoring, the ability to anchor probably does not involve a conformational change in the carboxy-terminal alpha helix itself [Phoenix93, Brandenburg02]. At least the final ten residues in the carboxy-terminus of PBP5 are needed to anchor it to the periplasmic face of the inner membrane, though eighteen are required for full binding [Pratt86, Jackson87]. Truncated, unbound PBP5 is water soluble, functional in vitro and can be crystallized [Ferreira88, vanderLinden93]. A naturally occurring, soluble PBP5 mutant has also been crystallized [Nicholas]. The carboxy-terminal 100 residues are not required for penicillin binding, but contribute to carboxypeptidase function, as the truncated mutant is only 40% active [vanderLinden93]. Carboxy-terminally truncated PBP5 can be made fully functional by the addition of the carboxy-terminal anchor from PBP6 or DacD, but not from PBP4 or an unrelated membrane protein. Fusion of the amino-terminal enzymatic domain of PBP5 to the carboxy-terminal beta sheet of PBP6 makes a functional protein, though the opposite fusion does not complement a dacA null [Nelson02]. Mosaic proteins composed of different portions of PBP5 and PBP6 were also constructed identifying residues 219 and 200 as important, but not required for PBP5 function [Ghosh03]. Both the PBP5 active site and membrane domain are required for maintenance of proper cell morphology [Nelson01a]. Note that all the residues in this paragraph are referred to by their position in the amino-terminally processed, mature form of PBP5 that lacks 29 residues from its amino-terminus.

The amino-terminus of PBP5 is sufficient to allow transport of a PBP5-OmpF fusion protein to the outer membrane, though this is not where PBP5 itself is localized [Jackson85]. Processing of PBP5 is SecA dependent [Jackson85].

A number of residues in PBP5 are necessary for its penicillin-binding and D-alanyl-D-alanine carboxypeptidase activities. Serine-44 is the active site that binds the β-lactam ring of penicillin [Nicholas85]. Mutations at this site and at lysine-213 lose both the penicillin-binding and carboxypeptidase activities except K213R and K213H mutations which still bind penicillin G [Malhotra92, vanderLinden94]. A mutant at lysine-47 has no carboxypeptidase function but continues to bind and hydrolyze penicillin, though the latter activity is greatly slowed [vanderLinden94]. Mutations in the SXN active-site motif at serine-110-glycine-111-asparagine-112 and at aspartate-175, histidine-216, and threonine-217 also lose carboxypeptidase function [vanderLinden94]. Cysteine-115 is not required for the carboxypeptidase function of PBP5 [Nicholas88]. The pH profile of PBP5 suggests K47 is the base for acylation and deacylation [Stefanova02].

PBP5 fractionates with PBP6 and PBP7/8 when inner membrane vesicles are separated on sucrose gradients [Jacoby88], with PBPs 1A, 1B, 2, and 3 when separated through agarose, and with PBPs 1-4 during chromatography through Sephacryl S-1000 [Leidenix89].

Purified PBP5 is a carboxypeptidase and removes the terminal D-alanine from UDP-MurNAc-pentapeptides [Amanuma80]. Purified PBP5 also binds penicillin G [Amanuma80], and the optimum pH for penicillin binding is 10 [Amaral86]. PBP5 activity is sensitive to penicillin G, is inhibited by Mg2+ and p-chloromercuribenzoate (pCMB), and protected from pCMB inhibition by 2-mercaptoethanol [Matsuhashi79]. The pH dependence of PBP5 activity has been examined over a broad pH range [Zhang07b]. PBP5 binds penicillin stoichiometrically [vanderLinden92]. PBP5 also binds penicillin V, cloxacillin, cefoxitin, moxalactam, and imipenem [Beadle01].

A dacA mutant lacks PBP5 and its D-alanyl-D-alanine carboxypeptidase 1A activity [Nishimura80]. A dacA mutant has increased crosslinkage because PBP5 is responsible for removal of the terminal D-alanine from peptidoglycan pentapeptides, the substrate of transpeptidases [Matsuhashi78, Hesek04]. A dacA dacB mutant has even more crosslinkages due to the deletion of D-alanine carboxypeptidase 1b (PBP4) in addition to PBP5 [Matsuhashi78]. Expression of dacA from a low copy number plasmid caused cells to grow as spheres [Stoker83]. Expression of dacA from a high copy number plasmid resulted in unstable transformants with odd morphology [Stoker83]. Mutations in dacA can lead to defective peptidoglycan morphology and failure to divide properly when the regulatory gene bolA is overexpressed or when additional mutations in other PBPs or FtsZ occur [Varma04, Meberg04, dePedro03, Santos02a, Nelson01a, Nelson00, Henderson97]. Deletion of dacA suppresses mutations in the cell division gene ftsK [Begg95, Draper98]. dacA mutants are viable, as are dacA dacC double mutants, dacA dacB dacC dacD quadruple mutants, and even strains with deletions of up to eight of the known penicillin-binding proteins at once, dacA included [Spratt80, BroomeSmith85a, Denome99, Baquero96]. A dacA pbpG mutant has increased levels of pentapepide muropeptides, increased muropeptide crosslinks, and decreased linkage of peptidoglycan to Braun lipoprotein [Varma07]. Inhibition of FtsZ and MreB in a dacA pbpG mutant results in cells that bloat in the middle but retain tubular extensions near preexisting poles where new peptidoglycan is not inserted [Varma07]. A dacA dacB amiC, dacA pbpG amiC, dacA amiA, or dacA amiB mutant exhibited increased chaining [Priyadarshini06]. A dacA amiA amiC mutant grows in twisted chains [Priyadarshini06]. A dacA mutant was isolated which lost D-alanine carboxypeptidase 1a activity but retained benzylpenicillin binding activity [Suzuki78]. Increased levels of PBP5 can reverse blocked cell division in a ftsI23 mutant by increasing the availability of tetrapeptides to be converted to tripeptides and utilized by PBP3 [Begg90].

BolA controls transcription of dacA and, through it, controls the peptidoglycan layer [Santos02a]. Overexpression of PBP5 has deleterious effects including lysis during early exponential phase growth, but overexpression of soluble PBP5 is possible and leads to formation of ordered PBP5 crystals within cells [Stoker83, Nelson01a, vanderLinden92a]. Nalidixic acid, novobiocin, oxolinic acit, and nitrofurantoin cause filamentation of E. coli and increased levels of PBP5 [Amaral86a].

Reviews: [Ghosh08]

Citations: [Spratt77a, Spratt80a, Amanuma84, delaRosa85, Chang90, Phoenix94, Gutheil00, Suvorov07, Shi08]

Locations: inner membrane

Map Position: [661,975 <- 663,186] (14.27 centisomes)
Length: 1212 bp / 403 aa

Molecular Weight of Polypeptide: 44.444 kD (from nucleotide sequence), 42.0 kD (experimental) [Spratt76 ]

Unification Links: ASAP:ABE-0002168 , CGSC:886 , DIP:DIP-47947N , EchoBASE:EB0197 , EcoGene:EG10201 , EcoliWiki:b0632 , Mint:MINT-1247273 , ModBase:P0AEB2 , OU-Microarray:b0632 , PortEco:dacA , PR:PRO_000022392 , Pride:P0AEB2 , Protein Model Portal:P0AEB2 , RefSeq:NP_415165 , RegulonDB:EG10201 , SMR:P0AEB2 , String:511145.b0632 , Swiss-Model:P0AEB2 , UniProt:P0AEB2

Relationship Links: InterPro:IN-FAMILY:IPR001967 , InterPro:IN-FAMILY:IPR012338 , InterPro:IN-FAMILY:IPR012907 , InterPro:IN-FAMILY:IPR015956 , InterPro:IN-FAMILY:IPR018044 , PDB:Structure:1hd8 , PDB:Structure:1NJ4 , PDB:Structure:1nzo , PDB:Structure:1NZU , PDB:Structure:1sdn , PDB:Structure:1z6f , PDB:Structure:3BEB , PDB:Structure:3BEC , PDB:Structure:3MZD , PDB:Structure:3MZE , PDB:Structure:3MZF , Pfam:IN-FAMILY:PF00768 , Pfam:IN-FAMILY:PF07943 , Prints:IN-FAMILY:PR00725 , Smart:IN-FAMILY:SM00936

In Paralogous Gene Group: 169 (4 members)

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0000270 - peptidoglycan metabolic process Inferred from experiment [Matsuhashi78, Amanuma80]
GO:0008360 - regulation of cell shape Inferred from experiment Inferred by computational analysis [UniProtGOA11a, Henderson97]
GO:0044036 - cell wall macromolecule metabolic process Inferred from experiment [Matsuhashi78, Amanuma80]
GO:0051301 - cell division Inferred from experiment [Begg90]
GO:0006508 - proteolysis Inferred by computational analysis [UniProtGOA11a, GOA01a]
GO:0009252 - peptidoglycan biosynthetic process Inferred by computational analysis [UniProtGOA12, UniProtGOA11a]
GO:0071555 - cell wall organization Inferred by computational analysis [UniProtGOA11a]
Molecular Function: GO:0004180 - carboxypeptidase activity Inferred from experiment Inferred by computational analysis [UniProtGOA11a, GOA01a, Matsuhashi78, Amanuma80]
GO:0008658 - penicillin binding Inferred from experiment [Amanuma80]
GO:0009002 - serine-type D-Ala-D-Ala carboxypeptidase activity Inferred from experiment Inferred by computational analysis [GOA01, GOA01a, Zhang07b, Matsuhashi79, vanderLinden92, Hesek04]
GO:0008233 - peptidase activity Inferred by computational analysis [UniProtGOA11a]
GO:0008800 - beta-lactamase activity Inferred by computational analysis [GOA01]
GO:0016787 - hydrolase activity Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005887 - integral component of plasma membrane Inferred from experiment [Spratt77a]
GO:0005886 - plasma membrane Inferred by computational analysis [UniProtGOA11, UniProtGOA11a, Jacoby88]
GO:0016020 - membrane Inferred by computational analysis [UniProtGOA11a]

MultiFun Terms: cell processes cell division
cell processes protection drug resistance/sensitivity

Essentiality data for dacA 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]

Credits:
Last-Curated ? 12-Nov-2008 by Johnson A , JCVI


Enzymatic reaction of: penicillinase (D-alanyl-D-alanine carboxypeptidase, fraction A; penicillin-binding protein 5)

EC Number: 3.5.2.6

a β-lactam[periplasmic space] + H2O[periplasmic space] <=> a substituted β-amino acid[periplasmic space]

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

Inhibitors (Unknown Mechanism): p-chloromercuribenzoate [Tamura76]


Enzymatic reaction of: D-alanyl-D-alanine carboxypeptidase

EC Number: 3.4.16.4

a lipid II[periplasmic space] + H2O[periplasmic space] <=> a N-acetylglucosamine--N-acetylmuramyl-(tetrapeptide) pyrophosphoryl-undecaprenol[periplasmic space] + D-alanine[periplasmic space]

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is physiologically favored in the direction shown.

Alternative Substrates for a lipid II: UDP-MurNAc-L-Ala-D-Glu-L-Lys-D-Ala-D-Ala [Tamura76 ] , UDP-MurNAC-L-ala-D-Glu-meso-DAP-D-ala-D-ala [Tamura76 ] , diacetyl-L-lys-D-ala-D-ala [Tamura76 ] , diacetyl-L-lys-D-ala-D-lac [Amanuma80 ]

Inhibitors (Unknown Mechanism): MgCl2 [Amanuma80] , amidino penicillin [Tamura76] , p-chloromercuribenzoate [Tamura76] , cephalosporin-C [Tamura76] , 6-APA [Tamura76] , penicillin G [Tamura76] , ampicillin [Tamura76]

pH(opt): 10 [Zhang07b]


Sequence Features

Feature Class Location Common Name Citations Comment
Signal-Sequence 1 -> 29 DacA signal sequence
[Waxman82a, Jackson85]
 
Chain 30 -> 403  
[UniProt09]
UniProt: D-alanyl-D-alanine carboxypeptidase dacA;
Active-Site 73  
[UniProt10]
UniProt: Acyl-ester intermediate;
Active-Site 76  
[UniProt10]
UniProt: Proton acceptor;
Active-Site 76, 242 Catalytic lysine residues
[Zhang07b, vanderLinden94]
These two lysines are both involved in catalysis, with Lys-76 taking part in proton transfer and Lys-242 serving as a substrate anchor.
Mutagenesis-Variant 101 -> 121  
[Nicholas03, UniProt11]
Alternate sequence: GNDAWATGNPVFKGSSLMFLK → missing; UniProt: Complete loss of enzyme activity. No effect on penicillin binding.
Extrinsic-Sequence-Variant 134  
[Nicholas03, Davies01, UniProt11]
Alternate sequence: G → D; UniProt: (in mutant dacA11191; inactive but still binds penicillin. Blocked in the release of the bound penicilloyl moiety; the mutant also fails to catalyze the D- alanine carboxypeptidase reaction as the hydrolysis of the acyl-enzyme formed with substrate is also blocked and the acyl- enzyme accumulates).
Active-Site 139  
[UniProt10]
Active-Site 140, 141, 139  
This is the probable active site for DacA [vanderLinden94]. A 2 Å-resolution structure of a modified DacA with disrupted function showes that the serine in the SXN motif is displaced, supporting the idea that this is the active site [Nicola05a].
Mutagenesis-Variant 213  
[Malhotra92, UniProt11]
Alternate sequence: K → X; UniProt: Complete loss of activity.
Alternate sequence: K → R; UniProt: Complete loss of enzyme activity. No effect on penicillin binding.
Amino-Acid-Sites-That-Bind 242  
[UniProt10]
UniProt: Substrate;
Transmembrane-Region 386 -> 403 DacA membrane anchor
[Jackson87]
 


Gene Local Context (not to scale): ?

Transcription Unit:

Notes:

History:
10/20/97 Gene b0632 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10201; confirmed by SwissProt match.


References

Amanuma80: Amanuma H, Strominger JL (1980). "Purification and properties of penicillin-binding proteins 5 and 6 from Escherichia coli membranes." J Biol Chem 255(23);11173-80. PMID: 7002918

Amanuma84: Amanuma H, Strominger JL (1984). "Purification and properties of penicillin-binding proteins 5 and 6 from the dacA mutant strain of Escherichia coli (JE 11191)." J Biol Chem 259(2);1294-8. PMID: 6363404

Amaral86: Amaral L, Lee Y, Schwarz U, Lorian V (1986). "Penicillin-binding site on the Escherichia coli cell envelope." J Bacteriol 167(2);492-5. PMID: 3090016

Amaral86a: Amaral L, Schwarz U, Lorian V (1986). "Penicillin-binding proteins of filaments of Escherichia coli induced by low concentrations of nalidixic acid, oxolinic acid, novobiocin or nitrofurantoin." Drugs Exp Clin Res 12(8);653-6. PMID: 3530676

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

Baquero96: Baquero MR, Bouzon M, Quintela JC, Ayala JA, Moreno F (1996). "dacD, an Escherichia coli gene encoding a novel penicillin-binding protein (PBP6b) with DD-carboxypeptidase activity." J Bacteriol 178(24);7106-11. PMID: 8955390

Beadle01: Beadle BM, Nicholas RA, Shoichet BK (2001). "Interaction energies between beta-lactam antibiotics and E. coli penicillin-binding protein 5 by reversible thermal denaturation." Protein Sci 10(6);1254-9. PMID: 11369864

Begg90: Begg KJ, Takasuga A, Edwards DH, Dewar SJ, Spratt BG, Adachi H, Ohta T, Matsuzawa H, Donachie WD (1990). "The balance between different peptidoglycan precursors determines whether Escherichia coli cells will elongate or divide." J Bacteriol 172(12);6697-703. PMID: 2254246

Begg95: Begg KJ, Dewar SJ, Donachie WD (1995). "A new Escherichia coli cell division gene, ftsK." J Bacteriol 177(21);6211-22. PMID: 7592387

Brandenburg02: Brandenburg K, Harris F, Phoenix DA, Seydel U (2002). "A study on the C-terminal membrane anchoring of Escherichia coli penicillin-binding protein 5." Biochem Biophys Res Commun 290(1);427-30. PMID: 11779187

BroomeSmith85a: Broome-Smith JK (1985). "Construction of a mutant of Escherichia coli that has deletions of both the penicillin-binding protein 5 and 6 genes." J Gen Microbiol 131(8);2115-8. PMID: 3903044

Chang90: Chang YH, Labgold MR, Richards JH (1990). "Altering enzymatic activity: recruitment of carboxypeptidase activity into an RTEM beta-lactamase/penicillin-binding protein 5 chimera." Proc Natl Acad Sci U S A 87(7);2823-7. PMID: 2181451

Davies01: Davies C, White SW, Nicholas RA (2001). "Crystal structure of a deacylation-defective mutant of penicillin-binding protein 5 at 2.3-A resolution." J Biol Chem 276(1);616-23. PMID: 10967102

delaRosa85: de la Rosa EJ, de Pedro MA, Vazquez D (1985). "Penicillin binding proteins: role in initiation of murein synthesis in Escherichia coli." Proc Natl Acad Sci U S A 82(17);5632-5. PMID: 3898066

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

dePedro03: de Pedro MA, Young KD, Holtje JV, Schwarz H (2003). "Branching of Escherichia coli cells arises from multiple sites of inert peptidoglycan." J Bacteriol 185(4);1147-52. PMID: 12562782

Draper98: Draper GC, McLennan N, Begg K, Masters M, Donachie WD (1998). "Only the N-terminal domain of FtsK functions in cell division." J Bacteriol 180(17);4621-7. PMID: 9721304

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

Ferreira88: Ferreira LC, Schwarz U, Keck W, Charlier P, Dideberg O, Ghuysen JM (1988). "Properties and crystallization of a genetically engineered, water-soluble derivative of penicillin-binding protein 5 of Escherichia coli K12." Eur J Biochem 171(1-2);11-6. PMID: 3276513

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

Ghosh03: Ghosh AS, Young KD (2003). "Sequences near the active site in chimeric penicillin binding proteins 5 and 6 affect uniform morphology of Escherichia coli." J Bacteriol 185(7);2178-86. PMID: 12644487

Ghosh08: Ghosh AS, Chowdhury C, Nelson DE (2008). "Physiological functions of D-alanine carboxypeptidases in Escherichia coli." Trends Microbiol 16(7);309-17. PMID: 18539032

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

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

Gutheil00: Gutheil WG, Stefanova ME, Nicholas RA (2000). "Fluorescent coupled enzyme assays for D-alanine: application to penicillin-binding protein and vancomycin activity assays." Anal Biochem 287(2);196-202. PMID: 11112264

Harris02a: Harris F, Brandenburg K, Seydel U, Phoenix D (2002). "Investigations into the mechanisms used by the C-terminal anchors of Escherichia coli penicillin-binding proteins 4, 5, 6 and 6b for membrane interaction." Eur J Biochem 269(23);5821-9. PMID: 12444970

Harris95: Harris F, Chatfield LK, Phoenix DA (1995). "Depletion of anionic phospholipids has no observable effect on the anchoring of penicillin binding protein 5 to the inner membrane of Escherichia coli." FEMS Microbiol Lett 129(2-3);215-20. PMID: 7607402

Harris97a: Harris F, Phoenix DA (1997). "An investigation into the ability of C-terminal homologues of Escherichia coli low molecular mass penicillin-binding proteins 4, 5 and 6 to undergo membrane interaction." Biochimie 79(4);171-4. PMID: 9242980

Harris98: Harris F, Demel R, de Kruijff B, Phoenix DA (1998). "An investigation into the lipid interactions of peptides corresponding to the C-terminal anchoring domains of Escherichia coli penicillin-binding proteins 4, 5 and 6." Biochim Biophys Acta 1415(1);10-22. PMID: 9858668

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

Hesek04: Hesek D, Suvorov M, Morio K, Lee M, Brown S, Vakulenko SB, Mobashery S (2004). "Synthetic peptidoglycan substrates for penicillin-binding protein 5 of Gram-negative bacteria." J Org Chem 69(3);778-84. PMID: 14750804

Jackson85: Jackson ME, Pratt JM, Stoker NG, Holland IB (1985). "An inner membrane protein N-terminal signal sequence is able to promote efficient localisation of an outer membrane protein in Escherichia coli." EMBO J 4(9);2377-83. PMID: 3908094

Jackson87: Jackson ME, Pratt JM (1987). "An 18 amino acid amphiphilic helix forms the membrane-anchoring domain of the Escherichia coli penicillin-binding protein 5." Mol Microbiol 1(1);23-8. PMID: 3330754

Jackson88: Jackson ME, Pratt JM (1988). "Analysis of the membrane-binding domain of penicillin-binding protein 5 of Escherichia coli." Mol Microbiol 2(5);563-8. PMID: 3054422

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

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

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

Malhotra92: Malhotra KT, Nicholas RA (1992). "Substitution of lysine 213 with arginine in penicillin-binding protein 5 of Escherichia coli abolishes D-alanine carboxypeptidase activity without affecting penicillin binding." J Biol Chem 267(16);11386-91. PMID: 1597468

Matsuhashi78: Matsuhashi M, Maruyama IN, Takagaki Y, Tamaki S, Nishimura Y, Hirota Y (1978). "Isolation of a mutant of Escherichia coli lacking penicillin-sensitive D-alanine carboxypeptidase IA." Proc Natl Acad Sci U S A 75(6);2631-5. PMID: 351612

Matsuhashi79: Matsuhashi M, Tamaki S, Curtis SJ, Strominger JL (1979). "Mutational evidence for identity of penicillin-binding protein 5 in Escherichia coli with the major D-alanine carboxypeptidase IA activity." J Bacteriol 137(1);644-7. PMID: 368033

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

Nelson00: Nelson DE, Young KD (2000). "Penicillin binding protein 5 affects cell diameter, contour, and morphology of Escherichia coli." J Bacteriol 182(6);1714-21. PMID: 10692378

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

Nelson02: Nelson DE, Ghosh AS, Paulson AL, Young KD (2002). "Contribution of membrane-binding and enzymatic domains of penicillin binding protein 5 to maintenance of uniform cellular morphology of Escherichia coli." J Bacteriol 184(13);3630-9. PMID: 12057958

Nicholas: Nicholas RA, Strominger JL "Relations between beta-lactamases and penicillin-binding proteins: beta-lactamase activity of penicillin-binding protein 5 from Escherichia coli." Rev Infect Dis 10(4);733-8. PMID: 3055172

Nicholas03: Nicholas RA, Krings S, Tomberg J, Nicola G, Davies C (2003). "Crystal structure of wild-type penicillin-binding protein 5 from Escherichia coli: implications for deacylation of the acyl-enzyme complex." J Biol Chem 278(52);52826-33. PMID: 14555648

Nicholas85: Nicholas RA, Ishino F, Park W, Matsuhashi M, Strominger JL (1985). "Purification and sequencing of the active site tryptic peptide from penicillin-binding protein 5 from the dacA mutant strain of Escherichia coli (TMRL 1222)." J Biol Chem 260(10);6394-7. PMID: 3888981

Nicholas88: Nicholas RA, Strominger JL (1988). "Site-directed mutants of a soluble form of penicillin-binding protein 5 from Escherichia coli and their catalytic properties." J Biol Chem 263(4);2034-40. PMID: 3276680

Nicola05: Nicola G, Peddi S, Stefanova M, Nicholas RA, Gutheil WG, Davies C (2005). "Crystal structure of Escherichia coli penicillin-binding protein 5 bound to a tripeptide boronic acid inhibitor: a role for Ser-110 in deacylation." Biochemistry 44(23);8207-17. PMID: 15938610

Nicola05a: Nicola G, Fedarovich A, Nicholas RA, Davies C (2005). "A large displacement of the SXN motif of Cys115-modified penicillin-binding protein 5 from Escherichia coli." Biochem J 392(Pt 1);55-63. PMID: 16038617

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Phoenix93: Phoenix DA, Pratt JM (1993). "Membrane interaction of Escherichia coli penicillin binding protein 5 is modulated by the ectomembranous domain." FEBS Lett 322(3);215-8. PMID: 8486152

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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