RegulonDB

Gene
Name:	ddlB
Synonym(s):	ECK0093, EG10214, b0092, ddl
Genome position(nucleotides):	102233 --> 103153
Strand:	forward
Sequence:	Get nucleotide sequence FastaFormat
GC content %:	51.57
External database links:

ASAP:	ABE-0000326
CGSC:	870
ECHOBASE:	EB0210
ECOLIHUB:	ddlB
OU-MICROARRAY:	b0092
STRING:	511145.b0092
COLOMBOS:	ddlB

Gene

Name:

ddlB

Synonym(s):

ECK0093, EG10214, b0092, ddl

Genome position(nucleotides):

102233 --> 103153

Strand:

forward

Sequence:

Get nucleotide sequence FastaFormat

GC content %:

51.57

External database links:

ASAP:

CGSC:

ECHOBASE:

ECOLIHUB:

OU-MICROARRAY:

STRING:

COLOMBOS:

Type

Positions

Sequence

Comment

2 -> 306

TDKIAVLLGGTSAEREVSLNSGAAVLAGLREGGIDAYPVDPKEVDVTQLKSMGFQKVFIALHGRGGEDGTLQGMLELMGLPYTGSGVMASALSMDKLRSKLLWQGAGLPVAPWVALTRAEFEKGLSDKQLAEISALGLPVIVKPSREGSSVGMSKVVAENALQDALRLAFQHDEEVLIEKWLSGPEFTVAILGEEILPSIRIQPSGTFYDYEAKYLSDETQYFCPAGLEASQEANLQALVLKAWTTLGCKGWGRIDVMLDSDGQFYLLEANTSPGMTSHSLVPMAARQAGMSFSQLVVRILELAD

UniProt: D-alanine--D-alanine ligase B.

4 -> 86

KIAVLLGGTSAEREVSLNSGAAVLAGLREGGIDAYPVDPKEVDVTQLKSMGFQKVFIALHGRGGEDGTLQGMLELMGLPYTGS

101 -> 303

KLLWQGAGLPVAPWVALTRAEFEKGLSDKQLAEISALGLPVIVKPSREGSSVGMSKVVAENALQDALRLAFQHDEEVLIEKWLSGPEFTVAILGEEILPSIRIQPSGTFYDYEAKYLSDETQYFCPAGLEASQEANLQALVLKAWTTLGCKGWGRIDVMLDSDGQFYLLEANTSPGMTSHSLVPMAARQAGMSFSQLVVRILE

UniProt: ATP-grasp.

103 -> 303

LWQGAGLPVAPWVALTRAEFEKGLSDKQLAEISALGLPVIVKPSREGSSVGMSKVVAENALQDALRLAFQHDEEVLIEKWLSGPEFTVAILGEEILPSIRIQPSGTFYDYEAKYLSDETQYFCPAGLEASQEANLQALVLKAWTTLGCKGWGRIDVMLDSDGQFYLLEANTSPGMTSHSLVPMAARQAGMSFSQLVVRILE

134 -> 189

ISALGLPVIVKPSREGSSVGMSKVVAENALQDALRLAFQHDEEVLIEKWLSGPEFT

UniProt: ATP.

Type

Positions

Sequence

Comment

2 -> 306

UniProt: D-alanine--D-alanine ligase B.

4 -> 86

KIAVLLGGTSAEREVSLNSGAAVLAGLREGGIDAYPVDPKEVDVTQLKSMGFQKVFIALHGRGGEDGTLQGMLELMGLPYTGS

101 -> 303

UniProt: ATP-grasp.

103 -> 303

134 -> 189

ISALGLPVIVKPSREGSSVGMSKVVAENALQDALRLAFQHDEEVLIEKWLSGPEFT

UniProt: ATP.

Multifun Terms (GenProtEC)

1 - metabolism --> 1.6 - biosynthesis of macromolecules (cellular constituents) --> 1.6.7 - murein (peptidoglycan)

6 - cell structure --> 6.2 - murein

Gene Ontology Terms (GO)

cellular_component

GO:0005737 - cytoplasm
GO:0005829 - cytosol

molecular_function

GO:0046872 - metal ion binding
GO:0016874 - ligase activity
GO:0000166 - nucleotide binding
GO:0005524 - ATP binding
GO:0008716 - D-alanine-D-alanine ligase activity
GO:0042803 - protein homodimerization activity

biological_process

GO:0009252 - peptidoglycan biosynthetic process
GO:0008360 - regulation of cell shape
GO:0071555 - cell wall organization

Transcriptional Regulation
	Display Regulation
Repressed by:	MraZ, LexA, PdhR

Transcriptional Regulation

Display Regulation

Repressed by:

MraZ, LexA, PdhR

Type	Name	Post Left	Strand	Notes	Evidence (Confirmed, Strong, Weak)	References
promoter	TSS_172	100621	forward	nd	[RS-EPT-CBR]	[13]
promoter	TSS_173 (cluster)	102049	forward	nd	[RS-EPT-CBR]	[13]
promoter	TSS_174	102679	forward	nd	[RS-EPT-CBR]	[13]
promoter	TSS_175	102865	forward	nd	[RS-EPT-CBR]	[13]
promoter	TSS_176	102872	forward	nd	[RS-EPT-CBR]	[13]
promoter	TSS_177	103019	forward	nd	[RS-EPT-CBR]	[13]
promoter	TSS_178	103024	forward	nd	[RS-EPT-CBR]	[13]
promoter	TSS_179 (cluster)	103028	forward	nd	[RS-EPT-CBR]	[13]
promoter	TSS_180	103133	forward	nd	[RS-EPT-CBR]	[13]
promoter	TSS_181	103608	forward	nd	[RS-EPT-CBR]	[13]
promoter	TSS_182	103889	forward	nd	[RS-EPT-CBR]	[13]
promoter	TSS_183	103960	forward	nd	[RS-EPT-CBR]	[13]

Type

Name

Post Left

Post Right

Strand

Notes

Evidence (Confirmed, Strong, Weak)

References

promoter

TSS_172

100621

forward

[RS-EPT-CBR]

[13]

promoter

TSS_173 (cluster)

102049

forward

[RS-EPT-CBR]

[13]

promoter

TSS_174

102679

forward

[RS-EPT-CBR]

[13]

promoter

TSS_175

102865

forward

[RS-EPT-CBR]

[13]

promoter

TSS_176

102872

forward

[RS-EPT-CBR]

[13]

promoter

TSS_177

103019

forward

[RS-EPT-CBR]

[13]

promoter

TSS_178

103024

forward

[RS-EPT-CBR]

[13]

promoter

TSS_179 (cluster)

103028

forward

[RS-EPT-CBR]

[13]

promoter

TSS_180

103133

forward

[RS-EPT-CBR]

[13]

promoter

TSS_181

103608

forward

[RS-EPT-CBR]

[13]

promoter

TSS_182

103889

forward

[RS-EPT-CBR]

[13]

promoter

TSS_183

103960

forward

[RS-EPT-CBR]

[13]

Evidence
[RS-EPT-CBR] RNA-seq using two enrichment strategies for primary transcripts and consistent biological replicates

Evidence

[RS-EPT-CBR] RNA-seq using two enrichment strategies for primary transcripts and consistent biological replicates

Reference(s)
[1] Batson S., de Chiara C., Majce V., Lloyd AJ., Gobec S., Rea D., Fulop V., Thoroughgood CW., Simmons KJ., Dowson CG., Fishwick CWG., de Carvalho LPS., Roper DI., 2017, Inhibition of D-Ala:D-Ala ligase through a phosphorylated form of the antibiotic D-cycloserine., Nat Commun 8(1):1939
[2] Besong GE., Bostock JM., Stubbings W., Chopra I., Roper DI., Lloyd AJ., Fishwick CW., Johnson AP., 2005, A de novo designed inhibitor of D-Ala-D-Ala ligase from E. coli., Angew Chem Int Ed Engl 44(39):6403-6
[3] Hersch SJ., Watanabe N., Stietz MS., Manera K., Kamal F., Burkinshaw B., Lam L., Pun A., Li M., Savchenko A., Dong TG., 2020, Envelope stress responses defend against type six secretion system attacks independently of immunity proteins., Nat Microbiol 5(5):706-714
[4] Kovac A., Konc J., Vehar B., Bostock JM., Chopra I., Janezic D., Gobec S., 2008, Discovery of new inhibitors of D-alanine:D-alanine ligase by structure-based virtual screening., J Med Chem 51(23):7442-8
[5] Kovac A., Majce V., Lenarsic R., Bombek S., Bostock JM., Chopra I., Polanc S., Gobec S., 2007, Diazenedicarboxamides as inhibitors of D-alanine-D-alanine ligase (Ddl)., Bioorg Med Chem Lett 17(7):2047-54
[6] Lugtenberg EJ., v Schijndel-van Dam A., 1973, Temperature-sensitive mutant of Escherichia coli K-12 with an impaired D-alanine:D-alanine ligase., J Bacteriol 113(1):96-104
[7] Murakami R., Muramatsu Y., Minami E., Masuda K., Sakaida Y., Endo S., Suzuki T., Ishida O., Takatsu T., Miyakoshi S., Inukai M., Isono F., 2009, A novel assay of bacterial peptidoglycan synthesis for natural product screening., J Antibiot (Tokyo) 62(3):153-8
[8] Putty S., Rai A., Jamindar D., Pagano P., Quinn CL., Mima T., Schweizer HP., Gutheil WG., 2011, Characterization of d-boroAla as a novel broad-spectrum antibacterial agent targeting d-Ala-d-Ala ligase., Chem Biol Drug Des 78(5):757-63
[9] Skedelj V., Arsovska E., Tomasic T., Kroflic A., Hodnik V., Hrast M., Bester-Rogac M., Anderluh G., Gobec S., Bostock J., Chopra I., O'Neill AJ., Randall C., Zega A., 2012, 6-Arylpyrido[2,3-d]pyrimidines as Novel ATP-Competitive Inhibitors of Bacterial D-Alanine:D-Alanine Ligase., PLoS One 7(8):e39922
[10] Sova M., Cadez G., Turk S., Majce V., Polanc S., Batson S., Lloyd AJ., Roper DI., Fishwick CW., Gobec S., 2009, Design and synthesis of new hydroxyethylamines as inhibitors of D-alanyl-D-lactate ligase (VanA) and D-alanyl-D-alanine ligase (DdlB)., Bioorg Med Chem Lett 19(5):1376-9
[11] Vehar B., Hrast M., Kovac A., Konc J., Mariner K., Chopra I., O'Neill A., Janezic D., Gobec S., 2011, Ellipticines and 9-acridinylamines as inhibitors of D-alanine:D-alanine ligase., Bioorg Med Chem 19(17):5137-46
[12] Wu D., Kong Y., Han C., Chen J., Hu L., Jiang H., Shen X., 2008, D-Alanine:D-alanine ligase as a new target for the flavonoids quercetin and apigenin., Int J Antimicrob Agents 32(5):421-6
[13] Salgado H, Peralta-Gil M, Gama-Castro S, Santos-Zavaleta A, Muñiz-Rascado L, García-Sotelo JS, Weiss V, Solano-Lira H, Martínez-Flores I, Medina-Rivera A, Salgado-Osorio G, Alquicira-Hernández S, Alquicira-Hernández K, López-Fuentes A, Porrón-Sotelo L, Huerta AM, Bonavides-Martínez C, Balderas-Martínez YI, Pannier L, Olvera M, Labastida A, Jiménez-Jacinto V, Vega-Alvarado L, Del Moral-Chávez V, Hernández-Alvarez A, Morett E, Collado-Vides J., 2012, RegulonDB v8.0: omics data sets, evolutionary conservation, regulatory phrases, cross-validated gold standards and more., Nucleic Acids Res.

Reference(s)

[1] Batson S., de Chiara C., Majce V., Lloyd AJ., Gobec S., Rea D., Fulop V., Thoroughgood CW., Simmons KJ., Dowson CG., Fishwick CWG., de Carvalho LPS., Roper DI., 2017, Inhibition of D-Ala:D-Ala ligase through a phosphorylated form of the antibiotic D-cycloserine., Nat Commun 8(1):1939

[2] Besong GE., Bostock JM., Stubbings W., Chopra I., Roper DI., Lloyd AJ., Fishwick CW., Johnson AP., 2005, A de novo designed inhibitor of D-Ala-D-Ala ligase from E. coli., Angew Chem Int Ed Engl 44(39):6403-6

[3] Hersch SJ., Watanabe N., Stietz MS., Manera K., Kamal F., Burkinshaw B., Lam L., Pun A., Li M., Savchenko A., Dong TG., 2020, Envelope stress responses defend against type six secretion system attacks independently of immunity proteins., Nat Microbiol 5(5):706-714

[4] Kovac A., Konc J., Vehar B., Bostock JM., Chopra I., Janezic D., Gobec S., 2008, Discovery of new inhibitors of D-alanine:D-alanine ligase by structure-based virtual screening., J Med Chem 51(23):7442-8

[5] Kovac A., Majce V., Lenarsic R., Bombek S., Bostock JM., Chopra I., Polanc S., Gobec S., 2007, Diazenedicarboxamides as inhibitors of D-alanine-D-alanine ligase (Ddl)., Bioorg Med Chem Lett 17(7):2047-54

[6] Lugtenberg EJ., v Schijndel-van Dam A., 1973, Temperature-sensitive mutant of Escherichia coli K-12 with an impaired D-alanine:D-alanine ligase., J Bacteriol 113(1):96-104

[7] Murakami R., Muramatsu Y., Minami E., Masuda K., Sakaida Y., Endo S., Suzuki T., Ishida O., Takatsu T., Miyakoshi S., Inukai M., Isono F., 2009, A novel assay of bacterial peptidoglycan synthesis for natural product screening., J Antibiot (Tokyo) 62(3):153-8

[8] Putty S., Rai A., Jamindar D., Pagano P., Quinn CL., Mima T., Schweizer HP., Gutheil WG., 2011, Characterization of d-boroAla as a novel broad-spectrum antibacterial agent targeting d-Ala-d-Ala ligase., Chem Biol Drug Des 78(5):757-63

[9] Skedelj V., Arsovska E., Tomasic T., Kroflic A., Hodnik V., Hrast M., Bester-Rogac M., Anderluh G., Gobec S., Bostock J., Chopra I., O'Neill AJ., Randall C., Zega A., 2012, 6-Arylpyrido[2,3-d]pyrimidines as Novel ATP-Competitive Inhibitors of Bacterial D-Alanine:D-Alanine Ligase., PLoS One 7(8):e39922

[10] Sova M., Cadez G., Turk S., Majce V., Polanc S., Batson S., Lloyd AJ., Roper DI., Fishwick CW., Gobec S., 2009, Design and synthesis of new hydroxyethylamines as inhibitors of D-alanyl-D-lactate ligase (VanA) and D-alanyl-D-alanine ligase (DdlB)., Bioorg Med Chem Lett 19(5):1376-9

[11] Vehar B., Hrast M., Kovac A., Konc J., Mariner K., Chopra I., O'Neill A., Janezic D., Gobec S., 2011, Ellipticines and 9-acridinylamines as inhibitors of D-alanine:D-alanine ligase., Bioorg Med Chem 19(17):5137-46

[12] Wu D., Kong Y., Han C., Chen J., Hu L., Jiang H., Shen X., 2008, D-Alanine:D-alanine ligase as a new target for the flavonoids quercetin and apigenin., Int J Antimicrob Agents 32(5):421-6

[13] Salgado H, Peralta-Gil M, Gama-Castro S, Santos-Zavaleta A, Muñiz-Rascado L, García-Sotelo JS, Weiss V, Solano-Lira H, Martínez-Flores I, Medina-Rivera A, Salgado-Osorio G, Alquicira-Hernández S, Alquicira-Hernández K, López-Fuentes A, Porrón-Sotelo L, Huerta AM, Bonavides-Martínez C, Balderas-Martínez YI, Pannier L, Olvera M, Labastida A, Jiménez-Jacinto V, Vega-Alvarado L, Del Moral-Chávez V, Hernández-Alvarez A, Morett E, Collado-Vides J., 2012, RegulonDB v8.0: omics data sets, evolutionary conservation, regulatory phrases, cross-validated gold standards and more., Nucleic Acids Res.