EzCatDB: M00347
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DB codeM00347
RLCP classification3.113.90040.334 : Transfer
CATH domainDomain 13.40.50.980 : Rossmann foldCatalytic domain
Domain 23.40.50.980 : Rossmann foldCatalytic domain
Domain 32.30.38.10 : Luciferase; domain 3Catalytic domain
Domain 43.30.300.30 : GMP Synthetase; Chain A, domain 3Catalytic domain
Domain 51.10.1200.10 : Non-ribosomal Peptide Synthetase Peptidyl Carrier Protein; Chain A
E.C.6.1.1.13

CATH domainRelated DB codes (homologues)
1.10.1200.10 : Non-ribosomal Peptide Synthetase Peptidyl Carrier Protein; Chain AU00001
2.30.38.10 : Luciferase; domain 3M00009,M00170
3.30.300.30 : GMP Synthetase; Chain A, domain 3M00009,M00170
3.40.50.980 : Rossmann foldM00009,M00170

Enzyme Name
UniProtKBKEGG

Q81G39P39581Q99ZA6Q5XBN5Q03AZ2P35854Q81G41P39579P63959Q5XBN7Q03AZ0P55153P39580P35855P39578P55154
Protein nameD-alanine--poly(phosphoribitol) ligase subunit 1D-alanine--poly(phosphoribitol) ligase subunit 1D-alanine--poly(phosphoribitol) ligase subunit 1D-alanine--poly(phosphoribitol) ligase subunit 1D-alanine--poly(phosphoribitol) ligase subunit 1D-alanine--poly(phosphoribitol) ligase subunit 1D-alanine--poly(phosphoribitol) ligase subunit 2D-alanine--poly(phosphoribitol) ligase subunit 2D-alanine--poly(phosphoribitol) ligase subunit 2D-alanine--poly(phosphoribitol) ligase subunit 2D-alanine--poly(phosphoribitol) ligase subunit 2D-alanine--poly(phosphoribitol) ligase subunit 2Protein dltBProtein dltBProtein dltDProtein dltDD-Alanine---poly(phosphoribitol) ligase
D-Alanyl-poly(phosphoribitol) synthetase
D-Alanine: membrane acceptor ligase
D-Alanine-D-alanyl carrier protein ligase
D-Alanine-membrane acceptor ligase
D-Alanine-activating enzyme
SynonymsEC 6.1.1.13
D-alanine-activating enzyme
DAE
D-alanine-D-alanyl carrier protein ligase
DCL
EC 6.1.1.13
D-alanine-activating enzyme
DAE
D-alanine-D-alanyl carrier protein ligase
DCL
EC 6.1.1.13
D-alanine-activating enzyme
DAE
D-alanine-D-alanyl carrier protein ligase
DCL
EC 6.1.1.13
D-alanine-activating enzyme
DAE
D-alanine-D-alanyl carrier protein ligase
DCL
EC 6.1.1.13
D-alanine-activating enzyme
DAE
D-alanine-D-alanyl carrier protein ligase
DCL
EC 6.1.1.13
D-alanine-activating enzyme
DAE
D-alanine-D-alanyl carrier protein ligase
DCL
EC 6.1.1.13
D-alanyl carrier protein
DCP
EC 6.1.1.13
D-alanyl carrier protein
DCP
EC 6.1.1.13
D-alanyl carrier protein
DCP
EC 6.1.1.13
D-alanyl carrier protein
DCP
EC 6.1.1.13
D-alanyl carrier protein
DCP
EC 6.1.1.13
D-alanyl carrier protein
DCP
NoneBasic membrane protein
BMP
NoneNone
RefSeqNP_831153.1 (Protein)
NC_004722.1 (DNA/RNA sequence)
NP_391729.1 (Protein)
NC_000964.3 (DNA/RNA sequence)
NP_269435.1 (Protein)
NC_002737.1 (DNA/RNA sequence)
YP_282436.1 (Protein)
NC_007297.1 (DNA/RNA sequence)
YP_060361.1 (Protein)
NC_006086.1 (DNA/RNA sequence)
YP_806072.1 (Protein)
NC_008526.1 (DNA/RNA sequence)

NP_831151.1 (Protein)
NC_004722.1 (DNA/RNA sequence)
NP_391731.1 (Protein)
NC_000964.3 (DNA/RNA sequence)
NP_269433.1 (Protein)
NC_002737.1 (DNA/RNA sequence)
YP_282434.1 (Protein)
NC_007297.1 (DNA/RNA sequence)
YP_060359.1 (Protein)
NC_006086.1 (DNA/RNA sequence)
YP_806074.1 (Protein)
NC_008526.1 (DNA/RNA sequence)

NP_391730.1 (Protein)
NC_000964.3 (DNA/RNA sequence)

NP_391732.1 (Protein)
NC_000964.3 (DNA/RNA sequence)

PfamPF00501 (AMP-binding)
[Graphical view]
PF00501 (AMP-binding)
[Graphical view]
PF00501 (AMP-binding)
[Graphical view]
PF00501 (AMP-binding)
[Graphical view]
PF00501 (AMP-binding)
PF13193 (DUF4009)
[Graphical view]
PF00501 (AMP-binding)
PF13193 (DUF4009)
[Graphical view]
PF00550 (PP-binding)
[Graphical view]
PF00550 (PP-binding)
[Graphical view]
PF00550 (PP-binding)
[Graphical view]
PF00550 (PP-binding)
[Graphical view]
PF00550 (PP-binding)
[Graphical view]
PF00550 (PP-binding)
[Graphical view]
PF03062 (MBOAT)
[Graphical view]
PF03062 (MBOAT)
[Graphical view]
PF04914 (DltD_C)
PF04918 (DltD_M)
PF04915 (DltD_N)
[Graphical view]
PF04918 (DltD_M)
PF04915 (DltD_N)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00473D-Alanine metabolism

UniProtKB:Accession NumberQ81G39P39581Q99ZA6Q5XBN5Q03AZ2P35854Q81G41P39579P63959Q5XBN7Q03AZ0P55153P39580P35855P39578P55154
Entry nameDLTA_BACCRDLTA_BACSUDLTA_STRP1DLTA_STRP6DLTA_LACC3DLTA_LACRHDLTC_BACCRDLTC_BACSUDLTC_STRP1DLTC_STRP6DLTC_LACC3DLTC_LACRHDLTB_BACSUDLTB_LACRHDLTD_BACSUDLTD_LACRH
ActivityATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate).ATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate).ATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate).ATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate).ATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate).ATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate).ATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate).ATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate).ATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate).ATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate).ATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate).ATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate).



Subunit















Subcellular locationCytoplasm (Probable).Cytoplasm (Probable).Cytoplasm (Probable).Cytoplasm (Probable).Cytoplasm (Probable).Cytoplasm (Probable).









Cofactor
















Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProductsintermediates
KEGG-idC00305C01134C00002C00133C00653C06042C00020C00013C04260L00075I00128I00131
CompoundMagnesiumPhosphopantetheineATPD-alaninepoly(ribitol phosphate)Lipoteichoic acidAMPdiphosphateO-D-alanyl-poly(ribitol phosphate)D-alanyl-lipoteichoic acidD-alanine adenylatePeptidyl-Ser-phosphopantetheine-S-D-alanine
Typedivalent metal (Ca2+, Mg2+)carbohydrate,peptide/protein,phosphate group/phosphate ion,sulfhydryl groupamine group,nucleotideamino acidscarbohydrate,phosphate group/phosphate ion,polysaccharidecarbohydrate,lipid,phosphate group/phosphate ion,polysaccharideamine group,nucleotidephosphate group/phosphate ionamino acids,carbohydrate,phosphate group/phosphate ion,polysaccharideamino acids,carbohydrate,lipid,phosphate group/phosphate ion,polysaccharide

ChEBI18420
4222
15422
15570
57416


16027
29888




PubChem888
115254
5957
7311725
71080


6083
21961011
1023




                    
3dhvA01UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3fccA01UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3fceA01UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3e7wA01UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3e7xA01UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3lgxA01UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3lgxB01UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3lgxC01UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3lgxD01UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3l8cA01UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3l8cB01UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3dhvA02UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundBound:DAL-AMPUnbound
3fccA02Bound:_MGUnboundBound:ATPUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3fceA02Analogue:_CAUnboundBound:ATPUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3e7wA02UnboundUnboundUnboundUnboundUnboundUnboundBound:AMPUnboundUnboundUnboundUnboundUnbound
3e7xA02UnboundUnboundUnboundUnboundUnboundUnboundBound:AMPUnboundUnboundUnboundUnboundUnbound
3lgxA02UnboundUnboundBound:ATPUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3lgxB02UnboundUnboundBound:ATPUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3lgxC02UnboundUnboundBound:ATPUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3lgxD02UnboundUnboundBound:ATPUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3l8cA02UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3l8cB02UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3dhvA03UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3fccA03UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3fceA03UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3e7wA03UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3e7xA03UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3lgxA03UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3lgxB03UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3lgxC03UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3lgxD03UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3l8cA03UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3l8cB03UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3dhvA04UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3fccA04UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3fceA04UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3e7wA04UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3e7xA04UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3lgxA04UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3lgxB04UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3lgxC04UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3lgxD04UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3l8cA04UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
3l8cB04UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1hqbA00UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound
1dv5A00UnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
Literature [5], [6]
pdbCatalytic residuesCofactor-binding residuesMain-chain involved in catalysiscomment
            
3dhvA01LYS 160
 
SER 153
invisible 154-158
3fccA01LYS 160
 
SER 153
invisible 155-158
3fceA01LYS 160
 
SER 153
invisible 155-158
3e7wA01LYS 159
 
SER 152
 
3e7xA01LYS 159
 
SER 152
 
3lgxA01LYS 156
 
SER 149
invisible 150-151
3lgxB01LYS 156
 
SER 149
invisible 150-152
3lgxC01LYS 156
 
SER 149
invisible 150-151
3lgxD01LYS 156
 
SER 149
invisible 150-151
3l8cA01LYS 156
 
SER 149
invisible 150-152
3l8cB01LYS 156
 
SER 149
 
3dhvA02 
GLU 298(Magnesium binding)
THR 297
 
3fccA02 
GLU 298(Magnesium binding)
THR 297
 
3fceA02 
GLU 298(Magnesium binding)
THR 297
 
3e7wA02 
GLU 297(Magnesium binding)
THR 296
 
3e7xA02 
GLU 297(Magnesium binding)
THR 296
 
3lgxA02 
GLU 296(Magnesium binding)
THR 295
 
3lgxB02 
GLU 296(Magnesium binding)
THR 295
 
3lgxC02 
GLU 296(Magnesium binding)
THR 295
 
3lgxD02 
GLU 296(Magnesium binding)
THR 295
 
3l8cA02 
GLU 296(Magnesium binding)
THR 295
 
3l8cB02 
GLU 296(Magnesium binding)
THR 295
 
3dhvA03ARG 397
 
 
 
3fccA03ARG 397
 
 
 
3fceA03ARG 397
 
 
 
3e7wA03ARG 396
 
 
 
3e7xA03ARG 396
 
 
 
3lgxA03ARG 396
 
 
 
3lgxB03ARG 396
 
 
 
3lgxC03ARG 396
 
 
 
3lgxD03ARG 396
 
 
 
3l8cA03ARG 396
 
 
 
3l8cB03ARG 396
 
 
 
3dhvA04LYS 403;ARG 408;LYS 492
 
 
 
3fccA04LYS 403;ARG 408;LYS 492
 
 
 
3fceA04LYS 403;ARG 408;LYS 492
 
 
 
3e7wA04LYS 402;ARG 407;LYS 491
 
 
 
3e7xA04LYS 402;ARG 407;LYS 491
 
 
 
3lgxA04LYS 402;ARG 407;LYS 495
 
 
 
3lgxB04LYS 402;ARG 407;LYS 495
 
 
 
3lgxC04LYS 402;ARG 407;LYS 495
 
 
 
3lgxD04LYS 402;ARG 407;LYS 495
 
 
 
3l8cA04LYS 402;       ;LYS 495
 
 
invisible 403-407
3l8cB04LYS 402;ARG 407;LYS 495
 
 
 
1hqbA00 
SER 39(Phosphopantetheine covalently binding through phosphate)
 
 
1dv5A00 
SER 39(Phosphopantetheine covalently binding through phosphate)
 
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[5]Fig.4, Fig.5, p.32489-32491
[6]p.347-349, p.350-353

references
[1]
PubMed ID8300523
JournalJ Bacteriol
Year1994
Volume176
Pages681-90
AuthorsHeaton MP, Neuhaus FC
TitleRole of the D-alanyl carrier protein in the biosynthesis of D-alanyl-lipoteichoic acid.
[2]
PubMed ID7797557
JournalJ Biol Chem
Year1995
Volume270
Pages15598-606
AuthorsPerego M, Glaser P, Minutello A, Strauch MA, Leopold K, Fischer W
TitleIncorporation of D-alanine into lipoteichoic acid and wall teichoic acid in Bacillus subtilis. Identification of genes and regulation.
[3]
PubMed ID11434765
JournalBiochemistry
Year2001
Volume40
Pages7964-72
AuthorsVolkman BF, Zhang Q, Debabov DV, Rivera E, Kresheck GC, Neuhaus FC
TitleBiosynthesis of D-alanyl-lipoteichoic acid: the tertiary structure of apo-D-alanyl carrier protein.
Related PDB1hqb,1dv5
Related UniProtKBQ03AZ0,P55153
[4]
PubMed ID18847223
JournalBiochemistry
Year2008
Volume47
Pages11473-80
AuthorsDu L, He Y, Luo Y
TitleCrystal structure and enantiomer selection by D-alanyl carrier protein ligase DltA from Bacillus cereus.
Related PDB3dhv
Related UniProtKBQ81G39
[5]
PubMed ID18784082
JournalJ Biol Chem
Year2008
Volume283
Pages32484-91
AuthorsYonus H, Neumann P, Zimmermann S, May JJ, Marahiel MA, Stubbs MT
TitleCrystal structure of DltA. Implications for the reaction mechanism of non-ribosomal peptide synthetase adenylation domains.
Related PDB3e7w,3e7x
Related UniProtKBP39581
[6]
PubMed ID19324056
JournalJ Mol Biol
Year2009
Volume388
Pages345-55
AuthorsOsman KT, Du L, He Y, Luo Y
TitleCrystal structure of Bacillus cereus D-alanyl carrier protein ligase (DltA) in complex with ATP.
Related PDB3fcc,3fce
Related UniProtKBQ81G39
[7]
PubMed ID19896895
JournalInt J Med Microbiol
Year2010
Volume300
Pages148-54
AuthorsXia G, Kohler T, Peschel A
TitleThe wall teichoic acid and lipoteichoic acid polymers of Staphylococcus aureus.

comments
This enzyme performs D-alanylation of lipoteichoic acids, which are the components of cell walls for Gram-positive bacteria (see [4], [6] and [7]).
This enzyme is composed of four subunits, DltA (D-alanyl carrier protein ligase, or Dcl), DltC (D-alanyl carrier protein, or Dcp), DltB (an integral membrane protein), and DltD (a membrane-tethered protein via N-terminal transmembrane domain). Although the structures of DltA and DltC have been elucidated, the structures of the two membrane proteins have not been solved yet. The structure of DltC (PDB; 1hqb and 1dv5) must be similar to those with phosphopantetheine from plasmodium (PDB;2fq0 and 2fq2)
According to the literature [5] and [6], this enzyme catalyzes the following reactions:
(A) Transfer of AMP from ATP to D-alanine carboxylate, forming an intermediate, D-ala-AMP, and releasing diphosphate (by DltA):
(A0) The magnesim ion, bound to Glu298 (of 3dhv), stabilizes the negative charge on the leaving beta- and gamma-phosphate groups of ATP. Simultaneously, Arg397 stabilizes the beta-phosphate, whereas the mainchain amide of Ser153 stabilizes the gamma-phosphate group. Meanwhile, the mobile residue, Lys492, stabilizes the transferred alpha-phosphate of ATP, along with the mainchain amide of Thr297, and modulates/stabilizes the acceptor nucleophile, the carboxylate oxygen of D-alanine substrate.
(A1) The carboxylate of D-alanine makes a nucleophilic attack on the alpha-phosphate group of ATP, forming a transition state. The transferred phosphate and leaving diphosphate group can be stabilized by the positively charged residues and magnesium ion during the transition state. (SN2-like reaction).
(B) Transfer of D-alanine group to thiol group of phosphopantetheine, which is covalently bound to a serine sidechain of DltC:
As the complex structure of DltA and DltC has not been elucidated, the detailed mechanism of this reaction is not clear.
(C) Transfer of D-alanine to the hydroxyl group of Lipoteichoic acids:
Although it is not clear how DltB and DltD are involved in the transfer reaction, they seem to be required for hte translocation and incorporation of D-alanine into Lipoteichoic acids.

createdupdated
2012-03-272012-05-29


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 2008)
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)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2012 - March 2013)
Supported by the commission for the Development of Artificial Gene Synthesis Technology for Creating Innovative Biomaterial from the Ministry of Economy, Trade and Industry (METI) (October 2012 - )
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