spacer
spacer

PDBsum entry 3e7x

Go to PDB code: 
protein ligands links
Ligase PDB id
3e7x
Jmol
Contents
Protein chain
508 a.a. *
Ligands
AMP
Waters ×211
* Residue conservation analysis
PDB id:
3e7x
Name: Ligase
Title: Crystal structure of dlta: implications for the reaction mechanism of non-ribosomal peptide synthetase (nrps) adenylation domains
Structure: D-alanine--poly(phosphoribitol) ligase subunit 1. Chain: a. Synonym: dlta protein, d-alanine-activating enzyme, dae, d- alanine-d-alanyl carrier protein ligase, dcl. Engineered: yes
Source: Bacillus subtilis. Organism_taxid: 1423. Gene: dlta. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.60Å     R-factor:   0.179     R-free:   0.238
Authors: H.Yonus,P.Neumann,S.Zimmermann,J.J.May,M.A.Marahiel, M.T.Stubbs
Key ref:
H.Yonus et al. (2008). Crystal structure of DltA. Implications for the reaction mechanism of non-ribosomal peptide synthetase adenylation domains. J Biol Chem, 283, 32484-32491. PubMed id: 18784082 DOI: 10.1074/jbc.M800557200
Date:
19-Aug-08     Release date:   09-Sep-08    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P39581  (DLTA_BACSU) -  D-alanine--poly(phosphoribitol) ligase subunit 1
Seq:
Struc:
503 a.a.
508 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.6.1.1.13  - D-alanine--poly(phosphoribitol) ligase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + D-alanine + poly(ribitol phosphate) = AMP + diphosphate + O-D- alanyl-poly(ribitol phosphate)
ATP
+ D-alanine
+ poly(ribitol phosphate)
=
AMP
Bound ligand (Het Group name = AMP)
corresponds exactly
+ diphosphate
+ O-D- alanyl-poly(ribitol phosphate)
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     cytoplasm   1 term 
  Biological process     metabolic process   2 terms 
  Biochemical function     catalytic activity     6 terms  

 

 
    reference    
 
 
DOI no: 10.1074/jbc.M800557200 J Biol Chem 283:32484-32491 (2008)
PubMed id: 18784082  
 
 
Crystal structure of DltA. Implications for the reaction mechanism of non-ribosomal peptide synthetase adenylation domains.
H.Yonus, P.Neumann, S.Zimmermann, J.J.May, M.A.Marahiel, M.T.Stubbs.
 
  ABSTRACT  
 
DltA, the D-alanine:D-alanyl carrier protein ligase responsible for the initial step of lipoteichoic acid D-alanylation in Gram-positive bacteria, belongs to the adenylation domain superfamily, which also includes acetyl-CoA synthetase and the adenylation domains of non-ribosomal synthetases. The two-step reaction catalyzed by these enzymes (substrate adenylation followed by transfer to the reactive thiol group of CoA or the phosphopantheinyl prosthetic group of peptidyl carrier proteins) has been suggested to proceed via large scale rearrangements of structural domains within the enzyme. The structures of DltA reported here reveal the determinants for D-Ala substrate specificity and confirm that the peptidyl carrier protein-activating domains are able to adopt multiple conformational states, in this case corresponding to the thiolation reaction. Comparisons of available structures allow us to propose a mechanism whereby small perturbations of finely balanced metastable structural states would be able to direct an ordered formation of non-ribosomal synthetase products.
 
  Selected figure(s)  
 
Figure 2.
The specificity pocket of DltA with d-Ala (transparent ball and sticks) docked in analogy to phenylalanine binding to PheA (24) (see text for details). The residues lining the hydrophobic pocket together with a kink in the helix caused by Pro-204 restrict entry; the side chain of Cys-268, found in two alternative conformations, would deter binding of l-Ala.
Figure 3.
Comparison of pyrophosphatase activities of wild type (gray) and mutant C268A (black) DltA. Mutation of Cys-268 to Ala results in a relaxation of the substrate specificity, in particular of the stereo selectivity. Abu, amino butyric acid.
 
  The above figures are reprinted by permission from the ASBMB: J Biol Chem (2008, 283, 32484-32491) copyright 2008.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21338915 A.J.Hughes, and A.Keatinge-Clay (2011).
Enzymatic extender unit generation for in vitro polyketide synthase reactions: structural and functional showcasing of Streptomyces coelicolor MatB.
  Chem Biol, 18, 165-176.
PDB codes: 3nyq 3nyr
20411119 I.Sainis, D.Fokas, K.Vareli, A.G.Tzakos, V.Kounnis, and E.Briasoulis (2010).
Cyanobacterial cyclopeptides as lead compounds to novel targeted cancer drugs.
  Mar Drugs, 8, 629-657.  
19923209 T.V.Lee, L.J.Johnson, R.D.Johnson, A.Koulman, G.A.Lane, J.S.Lott, and V.L.Arcus (2010).
Structure of a eukaryotic nonribosomal peptide synthetase adenylation domain that activates a large hydroxamate amino acid in siderophore biosynthesis.
  J Biol Chem, 285, 2415-2427.
PDB code: 3ite
19636447 A.Koglin, and C.T.Walsh (2009).
Structural insights into nonribosomal peptide enzymatic assembly lines.
  Nat Prod Rep, 26, 987.  
  19610673 A.M.Gulick (2009).
Conformational dynamics in the Acyl-CoA synthetases, adenylation domains of non-ribosomal peptide synthetases, and firefly luciferase.
  ACS Chem Biol, 4, 811-827.  
19544569 M.B.Shah, C.Ingram-Smith, L.L.Cooper, J.Qu, Y.Meng, K.S.Smith, and A.M.Gulick (2009).
The 2.1 A crystal structure of an acyl-CoA synthetase from Methanosarcina acetivorans reveals an alternate acyl-binding pocket for small branched acyl substrates.
  Proteins, 77, 685-698.
PDB code: 3etc
19320426 R.Wu, A.S.Reger, X.Lu, A.M.Gulick, and D.Dunaway-Mariano (2009).
The mechanism of domain alternation in the acyl-adenylate forming ligase superfamily member 4-chlorobenzoate: coenzyme A ligase.
  Biochemistry, 48, 4115-4125.
PDB code: 3dlp
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.