EzCatDB: T00108

DB codeT00108
CATH domainDomain 13.40.50.20Catalytic domain
Domain 23.30.470.20Catalytic domain
Domain 33.30.1490.20Catalytic domain
E.C.6.3.2.4
CSA2dln

CATH domainRelated DB codes (homologues)
3.30.1490.20T00082,M00035,M00037,T00107
3.30.470.20T00082,D00298,M00035,M00037,M00051,T00107
3.40.50.20T00082,M00037,T00107

Enzyme Name
Swiss-protKEGG

P07862P71454
Protein nameD-alanine--D-alanine ligase B
D-alanine---D-alanine ligase
MurE synthetase [ambiguous]
alanine:alanine ligase (ADP-forming)
alanylalanine synthetase
SynonymsEC 6.3.2.4
D-alanylalanine synthetase B
D-Ala-D-Ala ligase B
D-Ala-D-Ala ligase2

KEGG pathways
MAP codePathways
MAP00473D-Alanine metabolism
MAP00550Peptidoglycan biosynthesis

Swiss-prot:Accession NumberP07862P71454
Entry nameDDLB_ECOLIP71454_LEUME
ActivityATP + 2 D-alanine = ADP + phosphate + D- alanyl-D-alanine.
SubunitMonomer.
Subcellular locationCytoplasm.
CofactorBinds 2 magnesium or manganese ions per subunit (By similarity).


CofactorsSubstratesProductsintermediates
KEGG-idC00305C00002C00133C00008C00009C00993C12021
CompoundMagnesiumATPD-AlanineADPOrthophosphateD-Alanyl-D-alanineD-alanyl acylphosphateTetrahedral transition-state
Typedivalent metal (Ca2+, Mg2+)amine group,nucleotideamino acidsamine group,nucleotidephosphate group/phosphate ionamino acids,amide group,amine group,carboxyl group

1ehiA01UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1ehiB01UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1iovA01UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1iowA01UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2dlnA01UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1ehiA02Bound:2x_MGUnboundUnboundBound:ADPUnboundUnboundUnboundAnalogue:PHY
1ehiB02UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1iovA02Bound:3x_MGUnboundUnboundBound:ADPUnboundUnboundUnboundAnalogue:POB
1iowA02Bound:2x_MGUnboundUnboundBound:ADPUnboundUnboundUnboundAnalogue:PHY
2dlnA02Bound:2x_MGUnboundUnboundBound:ADPUnboundUnboundUnboundAnalogue:PHY
1ehiA03UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1ehiB03UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1iovA03UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1iowA03UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
2dlnA03UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
PDB;1iov, 1iow, 2dln & Swiss-prot;P07862 & literature [7], [8], [14]
pdbCatalytic residuesCofactor-binding residuesMain-chain involved in catalysiscomment
1ehiA01GLU  16



1ehiB01GLU 416



1iovA01GLU  15



1iowA01GLU  15



2dlnA01GLU  15



1ehiA02LYS 260;       ;ARG 301
ASP 303(Magnesium-1);GLU 316(Magnesium-1 & -2);ASN 318(Magnesium-2)
GLY 322

1ehiB02       ;       ;ARG 701
ASP 703(Magnesium-1);GLU 716(Magnesium-1 & -2);ASN 718(Magnesium-2)
GLY 722
invisible 645-666
1iovA02LYS 215;TYR 216;ARG 255
ASP 257(Magnesium-1);GLU 270(Magnesium-1 & -2);ASN 272(Magnesium-2)
GLY 276

1iowA02LYS 215;       ;ARG 255
ASP 257(Magnesium-1);GLU 270(Magnesium-1 & -2);ASN 272(Magnesium-2)
GLY 276
mutant Y216F
2dlnA02LYS 215;TYR 216;ARG 255
ASP 257(Magnesium-1);GLU 270(Magnesium-1 & -2);ASN 272(Magnesium-2)
GLY 276

1ehiA03SER 186



1ehiB03SER 586



1iovA03SER 150



1iowA03SER 150



2dlnA03SER 150




References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[1]Fig.4, Fig.5, p.3714
[2]Scheme II
[4]Fig.1, p.5774
[7]Fig.5, Fig.6, p.4413
[8]Scheme 1, Scheme 2, p.2773-27764
[9]Scheme I3
[10]Eq.(11), Eq.(12), p.10469-10470
[14]p.2536-2537
[15]

[25]Fig.1, p.466, p.467-4682

references
[1]
PubMed ID3044448
JournalBiochemistry
Year1988
Volume27
Pages3709-14
AuthorsDuncan K, Walsh CT
TitleATP-dependent inactivation and slow binding inhibition of Salmonella typhimurium D-alanine:D-alanine ligase (ADP) by (aminoalkyl)phosphinate and aminophosphonate analogues of D-alanine.
[2]
PubMed ID2562853
JournalJ Med Chem
Year1989
Volume32
Pages165-70
AuthorsGreenlee WJ, Springer JP, Patchett AA
TitleSynthesis of an analogue of tabtoxinine as a potential inhibitor of D-alanine:D-alanine ligase (ADP forming).
[3]
PubMed ID2648004
JournalJ Mol Biol
Year1989
Volume205
Pages461-3
AuthorsKnox JR, Liu HS, Walsh CT, Zawadzke LE
TitleD-alanine-D-alanine ligase (ADP) from Salmonella typhimurium. Overproduction, purification, crystallization and preliminary X-ray analysis.
[4]
PubMed ID2200515
JournalBiochemistry
Year1990
Volume29
Pages5767-75
AuthorsMcDermott AE, Creuzet F, Griffin RG, Zawadzke LE, Ye QZ, Walsh CT
TitleRotational resonance determination of the structure of an enzyme-inhibitor complex: phosphorylation of an (aminoalkyl)phosphinate inhibitor of D-alanyl-D-alanine ligase by ATP.
[5]
PubMed ID1540152
JournalBiochem Biophys Res Commun
Year1992
Volume182
Pages1040-6
AuthorsPeters JM, Dalrymple BP, Jorgensen WK
TitleSequence of a putative glutathione synthetase II gene and flanking regions from Anaplasma centrale.
[6]
PubMed ID8251948
JournalProtein Sci
Year1993
Volume2
Pages1765-9
AuthorsWright GD, Walsh CT
TitleIdentification of a common protease-sensitive region in D-alanyl-D-alanine and D-alanyl-D-lactate ligases and photoaffinity labeling with 8-azido ATP.
[7]
CommentsX-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
Medline ID95025939
PubMed ID7939684
JournalScience
Year1994
Volume266
Pages439-43
AuthorsFan C, Moews PC, Walsh CT, Knox JR
TitleVancomycin resistance: structure of D-alanine:D-alanine ligase at 2.3 A resolution.
Related PDB2dln
Related Swiss-protP07862
[8]
PubMed ID7893688
JournalBiochemistry
Year1995
Volume34
Pages2768-76
AuthorsShi Y, Walsh CT
TitleActive site mapping of Escherichia coli D-Ala-D-Ala ligase by structure-based mutagenesis.
[9]
PubMed ID7862655
JournalProc Natl Acad Sci U S A
Year1995
Volume92
Pages1172-6
AuthorsFan C, Moews PC, Shi Y, Walsh CT, Knox JR
TitleA common fold for peptide synthetases cleaving ATP to ADP: glutathione synthetase and D-alanine:d-alanine ligase of Escherichia coli.
[10]
PubMed ID8756703
JournalBiochemistry
Year1996
Volume35
Pages10464-71
AuthorsPark IS, Lin CH, Walsh CT
TitleGain of D-alanyl-D-lactate or D-lactyl-D-alanine synthetase activities in three active-site mutants of the Escherichia coli D-alanyl-D-alanine ligase B.
[11]
PubMed ID8662022
JournalJ Mol Evol
Year1996
Volume42
Pages706-12
AuthorsEvers S, Casadewall B, Charles M, Dutka-Malen S, Galimand M, Courvalin P
TitleEvolution of structure and substrate specificity in D-alanine:D-alanine ligases and related enzymes.
[12]
PubMed ID8564538
JournalNat Struct Biol
Year1996
Volume3
Pages128-32
AuthorsArtymiuk PJ, Poirrette AR, Rice DW, Willett P
TitleBiotin carboxylase comes into the fold.
[13]
PubMed ID9010922
JournalProtein Eng
Year1996
Volume9
Pages1083-92
AuthorsMatsuda K, Mizuguchi K, Nishioka T, Kato H, Go N, Oda J
TitleCrystal structure of glutathione synthetase at optimal pH: domain architecture and structural similarity with other proteins.
[14]
CommentsX-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
Medline ID97207065
PubMed ID9054558
JournalBiochemistry
Year1997
Volume36
Pages2531-8
AuthorsFan C, Park IS, Walsh CT, Knox JR
TitleD-alanine:D-alanine ligase: phosphonate and phosphinate intermediates with wild type and the Y216F mutant.
Related PDB1iov,1iow
Related Swiss-protP07862
[15]
PubMed ID9083053
JournalJ Biol Chem
Year1997
Volume272
Pages9210-4
AuthorsPark IS, Walsh CT
TitleD-Alanyl-D-lactate and D-alanyl-D-alanine synthesis by D-alanyl-D-alanine ligase from vancomycin-resistant Leuconostoc mesenteroides. Effects of a phenylalanine 261 to tyrosine mutation.
[16]
PubMed ID9463376
JournalEMBO J
Year1998
Volume17
Pages977-84
AuthorsEsser L, Wang CR, Hosaka M, Smagula CS, Sudhof TC, Deisenhofer J
TitleSynapsin I is structurally similar to ATP-utilizing enzymes.
[17]
PubMed ID10082373
JournalProtein Sci
Year1998
Volume7
Pages1768-71
AuthorsDenessiouk KA, Lehtonen JV, Johnson MS
TitleEnzyme-mononucleotide interactions: three different folds share common structural elements for ATP recognition.
[18]
PubMed ID9605318
JournalProtein Sci
Year1998
Volume7
Pages1136-46
AuthorsDenessiouk KA, Lehtonen JV, Korpela T, Johnson MS
TitleTwo "unrelated" families of ATP-dependent enzymes share extensive structural similarities about their cofactor binding sites.
[19]
PubMed ID9551557
JournalStructure
Year1998
Volume6
Pages363-76
AuthorsLevdikov VM, Barynin VV, Grebenko AI, Melik-Adamyan WR, Lamzin VS, Wilson KS
TitleThe structure of SAICAR synthase: an enzyme in the de novo pathway of purine nucleotide biosynthesis.
[20]
PubMed ID10074467
JournalChem Biol
Year1999
Volume6
Pages177-87
AuthorsLessard IA, Walsh CT
TitleMutational analysis of active-site residues of the enterococcal D-ala-D-Ala dipeptidase VanX and comparison with Escherichia coli D-ala-D-Ala ligase and D-ala-D-Ala carboxypeptidase VanY.
[21]
PubMed ID10065705
JournalProtein Eng
Year1999
Volume12
Pages11-4
AuthorsKinoshita K, Sadanami K, Kidera A, Go N
TitleStructural motif of phosphate-binding site common to various protein superfamilies: all-against-all structural comparison of protein-mononucleotide complexes.
[22]
PubMed ID10903933
JournalChem Biol
Year2000
Volume7
Pages505-14
AuthorsHealy VL, Mullins LS, Li X, Hall SE, Raushel FM, Walsh CT
TitleD-Ala-D-X ligases: evaluation of D-alanyl phosphate intermediate by MIX, PIX and rapid quench studies.
[23]
PubMed ID10937441
JournalJ Mol Microbiol Biotechnol
Year2000
Volume2
Pages321-30
AuthorsPrevost M, Van Belle D, Tulkens PM, Courvalin P, Van Bambeke F
TitleModeling of Enterococcus faecalis D-alanine:D-alanine ligase: structure-based study of the active site in the wild-type enzyme and in glycopeptide-dependent mutants.
[24]
PubMed ID10713991
JournalProteins
Year2000
Volume38
Pages310-26
AuthorsDenessiouk KA, Johnson MS
TitleWhen fold is not important: a common structural framework for adenine and AMP binding in 12 unrelated protein families.
[25]
CommentsX-ray crystallography
PubMed ID10801495
JournalStructure Fold Des
Year2000
Volume8
Pages463-70
AuthorsKuzin AP, Sun T, Jorczak-Baillass J, Healy VL, Walsh CT, Knox JR
TitleEnzymes of vancomycin resistance: the structure of D-alanine-D-lactate ligase of naturally resistant Leuconostoc mesenteroides.
Related PDB1ehi
[26]
PubMed ID11274474
JournalProtein Sci
Year2001
Volume10
Pages836-44
AuthorsGholizadeh Y, Prevost M, Van Bambeke F, Casadewall B, Tulkens PM, Courvalin P
TitleSequencing of the ddl gene and modeling of the mutated D-alanine:D-alanine ligase in glycopeptide-dependent strains of Enterococcus faecium.

comments
This enzyme is homologous to Glutathione synthetase (Swiss-prot;P04425, T00107 in EzCatDB).
This enzyme catalyzes the following reactions (see [7], [8]):
(A) Transfer of phosphate group from ATP to carboxyl oxygen of D-alanine, forming an intermediate, D-alanyl acylphosphate:
(B) Transfer of acyl group from D-alanyl acylphosphate to amine group of the second D-alanine substrate, releasing inorganic phosphate:

createdupdated
2004-08-012009-02-26


Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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