DB code: M00347

RLCP classification 3.113.90040.334 : Transfer
CATH domain 3.40.50.980 : Rossmann fold Catalytic domain
3.40.50.980 : Rossmann fold Catalytic domain
2.30.38.10 : Luciferase; domain 3 Catalytic domain
3.30.300.30 : GMP Synthetase; Chain A, domain 3 Catalytic domain
1.10.1200.10 : Non-ribosomal Peptide Synthetase Peptidyl Carrier Protein; Chain A
E.C. 6.1.1.13
CSA
M-CSA
MACiE

CATH domain Related DB codes (homologues)
1.10.1200.10 : Non-ribosomal Peptide Synthetase Peptidyl Carrier Protein; Chain A U00001
2.30.38.10 : Luciferase; domain 3 M00009 M00170
3.30.300.30 : GMP Synthetase; Chain A, domain 3 M00009 M00170
3.40.50.980 : Rossmann fold M00009 M00170

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
Q81G39 D-alanine--poly(phosphoribitol) ligase subunit 1
EC 6.1.1.13
D-alanine-activating enzyme
DAE
D-alanine-D-alanyl carrier protein ligase
DCL
NP_831153.1 (Protein)
NC_004722.1 (DNA/RNA sequence)
PF00501 (AMP-binding)
[Graphical View]
P39581 D-alanine--poly(phosphoribitol) ligase subunit 1
EC 6.1.1.13
D-alanine-activating enzyme
DAE
D-alanine-D-alanyl carrier protein ligase
DCL
NP_391729.1 (Protein)
NC_000964.3 (DNA/RNA sequence)
PF00501 (AMP-binding)
[Graphical View]
Q99ZA6 D-alanine--poly(phosphoribitol) ligase subunit 1
EC 6.1.1.13
D-alanine-activating enzyme
DAE
D-alanine-D-alanyl carrier protein ligase
DCL
NP_269435.1 (Protein)
NC_002737.1 (DNA/RNA sequence)
YP_282436.1 (Protein)
NC_007297.1 (DNA/RNA sequence)
PF00501 (AMP-binding)
[Graphical View]
Q5XBN5 D-alanine--poly(phosphoribitol) ligase subunit 1
EC 6.1.1.13
D-alanine-activating enzyme
DAE
D-alanine-D-alanyl carrier protein ligase
DCL
YP_060361.1 (Protein)
NC_006086.1 (DNA/RNA sequence)
PF00501 (AMP-binding)
[Graphical View]
Q03AZ2 D-alanine--poly(phosphoribitol) ligase subunit 1
EC 6.1.1.13
D-alanine-activating enzyme
DAE
D-alanine-D-alanyl carrier protein ligase
DCL
YP_806072.1 (Protein)
NC_008526.1 (DNA/RNA sequence)
PF00501 (AMP-binding)
PF13193 (DUF4009)
[Graphical View]
P35854 D-alanine--poly(phosphoribitol) ligase subunit 1
EC 6.1.1.13
D-alanine-activating enzyme
DAE
D-alanine-D-alanyl carrier protein ligase
DCL
PF00501 (AMP-binding)
PF13193 (DUF4009)
[Graphical View]
Q81G41 D-alanine--poly(phosphoribitol) ligase subunit 2
EC 6.1.1.13
D-alanyl carrier protein
DCP
NP_831151.1 (Protein)
NC_004722.1 (DNA/RNA sequence)
PF00550 (PP-binding)
[Graphical View]
P39579 D-alanine--poly(phosphoribitol) ligase subunit 2
EC 6.1.1.13
D-alanyl carrier protein
DCP
NP_391731.1 (Protein)
NC_000964.3 (DNA/RNA sequence)
PF00550 (PP-binding)
[Graphical View]
P63959 D-alanine--poly(phosphoribitol) ligase subunit 2
EC 6.1.1.13
D-alanyl carrier protein
DCP
NP_269433.1 (Protein)
NC_002737.1 (DNA/RNA sequence)
YP_282434.1 (Protein)
NC_007297.1 (DNA/RNA sequence)
PF00550 (PP-binding)
[Graphical View]
Q5XBN7 D-alanine--poly(phosphoribitol) ligase subunit 2
EC 6.1.1.13
D-alanyl carrier protein
DCP
YP_060359.1 (Protein)
NC_006086.1 (DNA/RNA sequence)
PF00550 (PP-binding)
[Graphical View]
Q03AZ0 D-alanine--poly(phosphoribitol) ligase subunit 2
EC 6.1.1.13
D-alanyl carrier protein
DCP
YP_806074.1 (Protein)
NC_008526.1 (DNA/RNA sequence)
PF00550 (PP-binding)
[Graphical View]
P55153 D-alanine--poly(phosphoribitol) ligase subunit 2
EC 6.1.1.13
D-alanyl carrier protein
DCP
PF00550 (PP-binding)
[Graphical View]
P39580 Protein dltB
None NP_391730.1 (Protein)
NC_000964.3 (DNA/RNA sequence)
PF03062 (MBOAT)
[Graphical View]
P35855 Protein dltB
Basic membrane protein
BMP
PF03062 (MBOAT)
[Graphical View]
P39578 Protein dltD
None NP_391732.1 (Protein)
NC_000964.3 (DNA/RNA sequence)
PF04914 (DltD_C)
PF04918 (DltD_M)
PF04915 (DltD_N)
[Graphical View]
P55154 Protein dltD
None PF04918 (DltD_M)
PF04915 (DltD_N)
[Graphical View]

KEGG enzyme name
D-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

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
Q81G39 DLTA_BACCR ATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate). Cytoplasm (Probable).
P39581 DLTA_BACSU ATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate). Cytoplasm (Probable).
Q99ZA6 DLTA_STRP1 ATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate). Cytoplasm (Probable).
Q5XBN5 DLTA_STRP6 ATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate). Cytoplasm (Probable).
Q03AZ2 DLTA_LACC3 ATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate). Cytoplasm (Probable).
P35854 DLTA_LACRH ATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate). Cytoplasm (Probable).
Q81G41 DLTC_BACCR ATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate).
P39579 DLTC_BACSU ATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate).
P63959 DLTC_STRP1 ATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate).
Q5XBN7 DLTC_STRP6 ATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate).
Q03AZ0 DLTC_LACC3 ATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate).
P55153 DLTC_LACRH ATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D-alanyl-poly(ribitol phosphate).
P39580 DLTB_BACSU
P35855 DLTB_LACRH
P39578 DLTD_BACSU
P55154 DLTD_LACRH

KEGG Pathways
Map code Pathways E.C.
MAP00473 D-Alanine metabolism

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00305 C01134 C00002 C00133 C00653 C06042 C00020 C00013 C04260 L00075 I00128 I00131
E.C.
Compound Magnesium Phosphopantetheine ATP D-alanine poly(ribitol phosphate) Lipoteichoic acid AMP diphosphate O-D-alanyl-poly(ribitol phosphate) D-alanyl-lipoteichoic acid D-alanine adenylate Peptidyl-Ser-phosphopantetheine-S-D-alanine
Type divalent metal (Ca2+, Mg2+) carbohydrate,peptide/protein,phosphate group/phosphate ion,sulfhydryl group amine group,nucleotide amino acids carbohydrate,phosphate group/phosphate ion,polysaccharide carbohydrate,lipid,phosphate group/phosphate ion,polysaccharide amine group,nucleotide phosphate group/phosphate ion amino acids,carbohydrate,phosphate group/phosphate ion,polysaccharide amino acids,carbohydrate,lipid,phosphate group/phosphate ion,polysaccharide
ChEBI 18420
 18420
 		4222
 4222
 		15422
 15422
 		15570
 57416
 15570
 57416
 		16027
 16027
 		29888
 29888
PubChem 888
 888
 		115254
 115254
 		5957
 5957
 		71080
 7311725
 71080
 7311725
 		6083
 6083
 		1023
 21961011
 1023
 21961011
3dhvA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3fccA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3fceA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3e7wA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3e7xA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lgxA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lgxB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lgxC01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lgxD01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3l8cA01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3l8cB01 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3dhvA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Bound:DAL-AMP Unbound
3fccA02 Bound:_MG Unbound Bound:ATP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3fceA02 Analogue:_CA Unbound Bound:ATP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3e7wA02 Unbound Unbound Unbound Unbound Unbound Unbound Bound:AMP Unbound Unbound Unbound Unbound Unbound
3e7xA02 Unbound Unbound Unbound Unbound Unbound Unbound Bound:AMP Unbound Unbound Unbound Unbound Unbound
3lgxA02 Unbound Unbound Bound:ATP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lgxB02 Unbound Unbound Bound:ATP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lgxC02 Unbound Unbound Bound:ATP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lgxD02 Unbound Unbound Bound:ATP Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3l8cA02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3l8cB02 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3dhvA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3fccA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3fceA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3e7wA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3e7xA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lgxA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lgxB03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lgxC03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lgxD03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3l8cA03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3l8cB03 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3dhvA04 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3fccA04 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3fceA04 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3e7wA04 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3e7xA04 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lgxA04 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lgxB04 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lgxC04 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3lgxD04 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3l8cA04 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
3l8cB04 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1hqbA00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1dv5A00 Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
Literature [5], [6]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
3dhvA01 LYS 160 SER 153 invisible 154-158
3fccA01 LYS 160 SER 153 invisible 155-158
3fceA01 LYS 160 SER 153 invisible 155-158
3e7wA01 LYS 159 SER 152
3e7xA01 LYS 159 SER 152
3lgxA01 LYS 156 SER 149 invisible 150-151
3lgxB01 LYS 156 SER 149 invisible 150-152
3lgxC01 LYS 156 SER 149 invisible 150-151
3lgxD01 LYS 156 SER 149 invisible 150-151
3l8cA01 LYS 156 SER 149 invisible 150-152
3l8cB01 LYS 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
3dhvA03 ARG 397
3fccA03 ARG 397
3fceA03 ARG 397
3e7wA03 ARG 396
3e7xA03 ARG 396
3lgxA03 ARG 396
3lgxB03 ARG 396
3lgxC03 ARG 396
3lgxD03 ARG 396
3l8cA03 ARG 396
3l8cB03 ARG 396
3dhvA04 LYS 403;ARG 408;LYS 492
3fccA04 LYS 403;ARG 408;LYS 492
3fceA04 LYS 403;ARG 408;LYS 492
3e7wA04 LYS 402;ARG 407;LYS 491
3e7xA04 LYS 402;ARG 407;LYS 491
3lgxA04 LYS 402;ARG 407;LYS 495
3lgxB04 LYS 402;ARG 407;LYS 495
3lgxC04 LYS 402;ARG 407;LYS 495
3lgxD04 LYS 402;ARG 407;LYS 495
3l8cA04 LYS 402;;LYS 495 invisible 403-407
3l8cB04 LYS 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
References Sections No. of steps in catalysis
[5]
Fig.4, Fig.5, p.32489-32491
[6]
p.347-349, p.350-353

References
[1]
Resource
Comments
Medline ID
PubMed ID 8300523
Journal J Bacteriol
Year 1994
Volume 176
Pages 681-90
Authors Heaton MP, Neuhaus FC
Title Role of the D-alanyl carrier protein in the biosynthesis of D-alanyl-lipoteichoic acid.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 7797557
Journal J Biol Chem
Year 1995
Volume 270
Pages 15598-606
Authors Perego M, Glaser P, Minutello A, Strauch MA, Leopold K, Fischer W
Title Incorporation of D-alanine into lipoteichoic acid and wall teichoic acid in Bacillus subtilis. Identification of genes and regulation.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 11434765
Journal Biochemistry
Year 2001
Volume 40
Pages 7964-72
Authors Volkman BF, Zhang Q, Debabov DV, Rivera E, Kresheck GC, Neuhaus FC
Title Biosynthesis of D-alanyl-lipoteichoic acid: the tertiary structure of apo-D-alanyl carrier protein.
Related PDB 1hqb 1dv5
Related UniProtKB Q03AZ0 P55153
[4]
Resource
Comments
Medline ID
PubMed ID 18847223
Journal Biochemistry
Year 2008
Volume 47
Pages 11473-80
Authors Du L, He Y, Luo Y
Title Crystal structure and enantiomer selection by D-alanyl carrier protein ligase DltA from Bacillus cereus.
Related PDB 3dhv
Related UniProtKB Q81G39
[5]
Resource
Comments
Medline ID
PubMed ID 18784082
Journal J Biol Chem
Year 2008
Volume 283
Pages 32484-91
Authors Yonus H, Neumann P, Zimmermann S, May JJ, Marahiel MA, Stubbs MT
Title Crystal structure of DltA. Implications for the reaction mechanism of non-ribosomal peptide synthetase adenylation domains.
Related PDB 3e7w 3e7x
Related UniProtKB P39581
[6]
Resource
Comments
Medline ID
PubMed ID 19324056
Journal J Mol Biol
Year 2009
Volume 388
Pages 345-55
Authors Osman KT, Du L, He Y, Luo Y
Title Crystal structure of Bacillus cereus D-alanyl carrier protein ligase (DltA) in complex with ATP.
Related PDB 3fcc 3fce
Related UniProtKB Q81G39
[7]
Resource
Comments
Medline ID
PubMed ID 19896895
Journal Int J Med Microbiol
Year 2010
Volume 300
Pages 148-54
Authors Xia G, Kohler T, Peschel A
Title The wall teichoic acid and lipoteichoic acid polymers of Staphylococcus aureus.
Related PDB
Related UniProtKB

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.

Created Updated
2012-03-27 2012-05-29