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PDBsum entry 1u7z

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protein ligands Protein-protein interface(s) links
Ligase PDB id
1u7z
Jmol
Contents
Protein chains
216 a.a. *
Ligands
PMT ×3
Waters ×258
* Residue conservation analysis
PDB id:
1u7z
Name: Ligase
Title: Phosphopantothenoylcysteine synthetase from e. Coli, 4'- phosphopantothenoyl-cmp complex
Structure: Coenzyme a biosynthesis bifunctional protein coabc. Chain: a, b, c. Fragment: phosphopantothenoylcysteine synthetase(residues 181-406). Engineered: yes. Mutation: yes
Source: Escherichia coli. Organism_taxid: 562. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
2.30Å     R-factor:   0.196     R-free:   0.266
Authors: S.Stanitzek,M.A.Augustin,R.Huber,T.Kupke,S.Steinbacher
Key ref:
S.Stanitzek et al. (2004). Structural basis of CTP-dependent peptide bond formation in coenzyme A biosynthesis catalyzed by Escherichia coli PPC synthetase. Structure, 12, 1977-1988. PubMed id: 15530362 DOI: 10.1016/j.str.2004.08.007
Date:
04-Aug-04     Release date:   30-Nov-04    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
P0ABQ0  (COABC_ECOLI) -  Coenzyme A biosynthesis bifunctional protein CoaBC
Seq:
Struc:
406 a.a.
216 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class 1: E.C.4.1.1.36  - Phosphopantothenoylcysteine decarboxylase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Coenzyme A Biosynthesis (late stages)
      Reaction: N-((R)-4'-phosphopantothenoyl)-L-cysteine = pantotheine 4'-phosphate + CO2
N-((R)-4'-phosphopantothenoyl)-L-cysteine
= pantotheine 4'-phosphate
+ CO(2)
      Cofactor: FMN
FMN
   Enzyme class 2: E.C.6.3.2.5  - Phosphopantothenate--cysteine ligase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
      Reaction: CTP + (R)-4'-phosphopantothenate + L-cysteine = CMP + diphosphate + N-((R)-4'-phosphopantothenoyl)-L-cysteine
CTP
+ (R)-4'-phosphopantothenate
+ L-cysteine
=
CMP
Bound ligand (Het Group name = PMT)
matches with 53.00% similarity
+ diphosphate
+ N-((R)-4'-phosphopantothenoyl)-L-cysteine
Note, where more than one E.C. class is given (as above), each may correspond to a different protein domain or, in the case of polyprotein precursors, to a different mature protein.
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     coenzyme A biosynthetic process   2 terms 
  Biochemical function     FMN binding     3 terms  

 

 
    reference    
 
 
DOI no: 10.1016/j.str.2004.08.007 Structure 12:1977-1988 (2004)
PubMed id: 15530362  
 
 
Structural basis of CTP-dependent peptide bond formation in coenzyme A biosynthesis catalyzed by Escherichia coli PPC synthetase.
S.Stanitzek, M.A.Augustin, R.Huber, T.Kupke, S.Steinbacher.
 
  ABSTRACT  
 
Phosphopantothenoylcysteine (PPC) synthetase forms a peptide bond between 4'-phosphopantothenate and cysteine in coenzyme A biosynthesis. PPC synthetases fall into two classes: eukaryotic, ATP-dependent and eubacterial, CTP-dependent enzymes. We describe the first crystal structure of E. coli PPC synthetase as a prototype of bacterial, CTP-dependent PPC synthetases. Structures of the apo-form and the synthetase complexed with CTP, the activated acyl-intermediate, 4'-phosphopantothenoyl-CMP, and with the reaction product CMP provide snapshots along the reaction pathway and detailed insight into substrate binding and the reaction mechanism of peptide bond formation. Binding of the phosphopantothenate moiety of the acyl-intermediate in a cleft at the C-terminal end of the central beta sheet of the dinucleotide binding fold is accomplished by an otherwise flexible flap. A second disordered loop may control access of cysteine to the active site. The conservation of functionalities involved in substrate binding and catalysis provides insight into similarities and differences of prokaryotic and eukaryotic PPC synthetases.
 
  Selected figure(s)  
 
Figure 6.
Figure 6. Comparison of Bacterial and Human CoaB(A) Superposition of human (gold) and E. coli CoaB (blue). Human CoaB is a monofunctional dimer in solution and has an additional dimerization domain.(B) Comparison of nucleotide binding sites. The Ca-trace for ecCoaB is shown in blue, for the human enzyme in gold. The bound 4'-phosphophopantothenoyl-CMP in ecCoaB is shown as a ball-and-stick model. The larger binding pocket in the human enzyme is required to accommodate an adenosyl-moiety instead of a cytidyl-moiety.
 
  The above figure is reprinted by permission from Cell Press: Structure (2004, 12, 1977-1988) copyright 2004.  
  Figure was selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19902973 J.D.Patrone, J.Yao, N.E.Scott, and G.D.Dotson (2009).
Selective inhibitors of bacterial phosphopantothenoylcysteine synthetase.
  J Am Chem Soc, 131, 16340-16341.  
19182993 J.Yao, J.D.Patrone, and G.D.Dotson (2009).
Characterization and kinetics of phosphopantothenoylcysteine synthetase from Enterococcus faecalis.
  Biochemistry, 48, 2799-2806.  
16371361 T.Kupke, and W.Schwarz (2006).
4'-phosphopantetheine biosynthesis in Archaea.
  J Biol Chem, 281, 5435-5444.  
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.