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Ligase PDB id
1iov
Jmol
Contents
Protein chain
306 a.a. *
Ligands
ADP
POB
Metals
_MG ×3
Waters ×263
* Residue conservation analysis
PDB id:
1iov
Name: Ligase
Title: Complex of d-ala:d-ala ligase with adp and a phosphoryl phosphonate
Structure: D-ala\:d-ala ligase. Chain: a. Engineered: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562. Other_details: enzyme provided by c.T. Walsh, harvard med school. See zawadzke et al. Biochem. 30, p. 1673, 1991.
Biol. unit: Dimer (from PQS)
Resolution:
2.20Å     R-factor:   0.156     R-free:   0.204
Authors: J.R.Knox,P.C.Moews,C.Fan
Key ref:
C.Fan et al. (1997). D-alanine:D-alanine ligase: phosphonate and phosphinate intermediates with wild type and the Y216F mutant. Biochemistry, 36, 2531-2538. PubMed id: 9054558 DOI: 10.1021/bi962431t
Date:
20-Sep-96     Release date:   12-Feb-97    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P07862  (DDLB_ECOLI) -  D-alanine--D-alanine ligase B
Seq:
Struc: 		306 a.a.
306 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.6.3.2.4  - D-alanine--D-alanine ligase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway: 		Peptidoglycan Biosynthesis (Part 1)
      Reaction: ATP + 2 D-alanine = ADP + phosphate + D-alanyl-D-alanine
ATP
 + 2 × D-alanine
 =
ADP
Bound ligand (Het Group name = ADP)
corresponds exactly 		+ phosphate
 + D-alanyl-D-alanine
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cell wall   2 terms 
  Biological process     cell wall organization   3 terms 
  Biochemical function     catalytic activity     6 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi962431t Biochemistry 36:2531-2538 (1997)
PubMed id: 9054558  
 
 
D-alanine:D-alanine ligase: phosphonate and phosphinate intermediates with wild type and the Y216F mutant.
C.Fan, I.S.Park, C.T.Walsh, J.R.Knox.
 
  ABSTRACT  
 
The crystallographic structure of the D-alanine:D-alanine ligase of the ddlB gene of Escherichia coli complexed with a D-Ala-D-alpha-hydroxybutyrate phosphonate and the structure of the Y216F mutant ligase complexed with a D-Ala-D-Ala phosphinate have been determined to 2.2 and 1.9 A resolution, respectively, and refined to R factors of 0.156 and 0.158. In each complex the inhibitor has reacted with ATP to produce ADP and a tight-binding phosphorylated transition state intermediate. Comparison of these two structures with the known crystal structure of the phosphinate intermediate of the wild-type ligase shows no major conformational changes, but B factors indicate differences in mobility of loops covering the binding site. The weaker inhibition of the Y216F mutant by both inhibitors is thought to be due in part to the loss of an interloop hydrogen bond. A similar mechanism may account for poor inhibition of VanA, the homologous D-Ala:D-lactate ligase produced by vancomycin-resistant enterococci.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
19770507 Y.Kitamura, A.Ebihara, Y.Agari, A.Shinkai, K.Hirotsu, and S.Kuramitsu (2009).
Structure of D-alanine-D-alanine ligase from Thermus thermophilus HB8: cumulative conformational change and enzyme-ligand interactions.
  Acta Crystallogr D Biol Crystallogr, 65, 1098-1106.  
18266853 H.Barreteau, A.Kovac, A.Boniface, M.Sova, S.Gobec, and D.Blanot (2008).
Cytoplasmic steps of peptidoglycan biosynthesis.
  FEMS Microbiol Rev, 32, 168-207.  
18069798 Y.Zhang, R.H.White, and S.E.Ealick (2008).
Crystal structure and function of 5-formaminoimidazole-4-carboxamide ribonucleotide synthetase from Methanocaldococcus jannaschii.
  Biochemistry, 47, 205-217.
PDB codes: 2r7k 2r7l 2r7m 2r7n 2r84 2r85 2r86 2r87
17390395 G.Füser, and A.Steinbüchel (2007).
Analysis of genome sequences for genes of cyanophycin metabolism: identifying putative cyanophycin metabolizing prokaryotes.
  Macromol Biosci, 7, 278-296.  
  17768361 Y.Z.Lu, Y.Sheng, L.F.Li, D.W.Tang, X.Y.Liu, X.Zhao, Y.H.Liang, and X.D.Su (2007).
Crystallization and preliminary crystallographic analysis of D-alanine-D-alanine ligase from Streptococcus mutans.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 807-808.  
16251194 H.Arulanantham, N.J.Kershaw, K.S.Hewitson, C.E.Hughes, J.E.Thirkettle, and C.J.Schofield (2006).
ORF17 from the clavulanic acid biosynthesis gene cluster catalyzes the ATP-dependent formation of N-glycyl-clavaminic acid.
  J Biol Chem, 281, 279-287.  
16779845 J.H.Lee, Y.Na, H.E.Song, D.Kim, B.H.Park, S.H.Rho, Y.J.Im, M.K.Kim, G.B.Kang, D.S.Lee, and S.H.Eom (2006).
Crystal structure of the apo form of D-alanine: D-alanine ligase (Ddl) from Thermus caldophilus: a basis for the substrate-induced conformational changes.
  Proteins, 64, 1078-1082.
PDB code: 2fb9
17015835 S.Liu, J.S.Chang, J.T.Herberg, M.M.Horng, P.K.Tomich, A.H.Lin, and K.R.Marotti (2006).
Allosteric inhibition of Staphylococcus aureus D-alanine:D-alanine ligase revealed by crystallographic studies.
  Proc Natl Acad Sci U S A, 103, 15178-15183.
PDB codes: 2i80 2i87 2i8c
16041744 J.Hiratake (2005).
Enzyme inhibitors as chemical tools to study enzyme catalysis: rational design, synthesis, and applications.
  Chem Rec, 5, 209-228.  
14990577 A.Dinescu, T.R.Cundari, V.S.Bhansali, J.L.Luo, and M.E.Anderson (2004).
Function of conserved residues of human glutathione synthetase: implications for the ATP-grasp enzymes.
  J Biol Chem, 279, 22412-22421.  
11953435 J.B.Thoden, S.M.Firestine, S.J.Benkovic, and H.M.Holden (2002).
PurT-encoded glycinamide ribonucleotide transformylase. Accommodation of adenosine nucleotide analogs within the active site.
  J Biol Chem, 277, 23898-23908.
PDB codes: 1kj8 1kj9 1kji 1kjj 1kjq
12409610 M.T.Miller, B.O.Bachmann, C.A.Townsend, and A.C.Rosenzweig (2002).
The catalytic cycle of beta -lactam synthetase observed by x-ray crystallographic snapshots.
  Proc Natl Acad Sci U S A, 99, 14752-14757.
PDB codes: 1m1z 1mb9 1mbz 1mc1
11455601 K.A.Denessiouk, V.V.Rantanen, and M.S.Johnson (2001).
Adenine recognition: a motif present in ATP-, CoA-, NAD-, NADP-, and FAD-dependent proteins.
  Proteins, 44, 282-291.  
  10801495 A.P.Kuzin, T.Sun, J.Jorczak-Baillass, V.L.Healy, C.T.Walsh, and J.R.Knox (2000).
Enzymes of vancomycin resistance: the structure of D-alanine-D-lactate ligase of naturally resistant Leuconostoc mesenteroides.
  Structure, 8, 463-470.
PDB code: 1ehi
10908650 D.I.Roper, T.Huyton, A.Vagin, and G.Dodson (2000).
The molecular basis of vancomycin resistance in clinically relevant Enterococci: crystal structure of D-alanyl-D-lactate ligase (VanA).
  Proc Natl Acad Sci U S A, 97, 8921-8925.
PDB code: 1e4e
10913290 J.B.Thoden, S.Firestine, A.Nixon, S.J.Benkovic, and H.M.Holden (2000).
Molecular structure of Escherichia coli PurT-encoded glycinamide ribonucleotide transformylase.
  Biochemistry, 39, 8791-8802.
PDB codes: 1eyz 1ez1
10713991 K.A.Denessiouk, and M.S.Johnson (2000).
When fold is not important: a common structural framework for adenine and AMP binding in 12 unrelated protein families.
  Proteins, 38, 310-326.  
10903933 V.L.Healy, L.S.Mullins, X.Li, S.E.Hall, F.M.Raushel, and C.T.Walsh (2000).
D-Ala-D-X ligases: evaluation of D-alanyl phosphate intermediate by MIX, PIX and rapid quench studies.
  Chem Biol, 7, 505-514.  
10024021 J.V.Lehtonen, K.Denessiouk, A.C.May, and M.S.Johnson (1999).
Finding local structural similarities among families of unrelated protein structures: a generic non-linear alignment algorithm.
  Proteins, 34, 341-355.  
10417422 T.Huyton, and D.I.Roper (1999).
Crystallization and preliminary X-ray characterization of VanA from Enterococcus faecium BM4147: towards the molecular basis of bacterial resistance to the glycopeptide antibiotic vancomycin.
  Acta Crystallogr D Biol Crystallogr, 55, 1481-1483.  
  10082373 K.A.Denessiouk, J.V.Lehtonen, and M.S.Johnson (1998).
Enzyme-mononucleotide interactions: three different folds share common structural elements for ATP recognition.
  Protein Sci, 7, 1768-1771.  
  9605318 K.A.Denessiouk, J.V.Lehtonen, T.Korpela, and M.S.Johnson (1998).
Two "unrelated" families of ATP-dependent enzymes share extensive structural similarities about their cofactor binding sites.
  Protein Sci, 7, 1136-1146.  
9294159 I.S.Park, C.H.Lin, and C.T.Walsh (1997).
Bacterial resistance to vancomycin: overproduction, purification, and characterization of VanC2 from Enterococcus casseliflavus as a D-Ala-D-Ser ligase.
  Proc Natl Acad Sci U S A, 94, 10040-10044.  
  9425668 J.Trias, and E.M.Gordon (1997).
Innovative approaches to novel antibacterial drug discovery.
  Curr Opin Biotechnol, 8, 757-762.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.