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PDBsum entry 2a86

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protein ligands Protein-protein interface(s) links
Ligase PDB id
2a86
Jmol
Contents
Protein chains
288 a.a. *
Ligands
SO4
AMP ×2
BAL ×2
GOL ×5
EOH ×5
Waters ×313
* Residue conservation analysis
PDB id:
2a86
Name: Ligase
Title: Crystal structure of a pantothenate synthetase complexed wit beta-alanine
Structure: Pantoate--beta-alanine ligase. Chain: a, b. Synonym: pantothenate synthetase, pantoate activating enzym engineered: yes. Mutation: yes
Source: Mycobacterium tuberculosis. Organism_taxid: 1773. Gene: panc. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.
Biol. unit: Dimer (from PQS)
Resolution:
1.85Å     R-factor:   0.161     R-free:   0.195
Authors: S.Wang,D.Eisenberg,Tb Structural Genomics Consortium (Tbsgc)
Key ref:
S.Wang and D.Eisenberg (2006). Crystal structure of the pantothenate synthetase from Mycobacterium tuberculosis, snapshots of the enzyme in action. Biochemistry, 45, 1554-1561. PubMed id: 16460002 DOI: 10.1021/bi051873e
Date:
07-Jul-05     Release date:   21-Feb-06    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam  
P9WIL4  (PANC_MYCTO) -  Pantothenate synthetase
Seq:
Struc:
309 a.a.
288 a.a.*
Key:    Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.6.3.2.1  - Pantoate--beta-alanine ligase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

      Pathway:
Coenzyme A Biosynthesis (early stages)
      Reaction: ATP + (R)-pantoate + beta-alanine = AMP + diphosphate + (R)-pantothenate
ATP
+ (R)-pantoate
+
beta-alanine
Bound ligand (Het Group name = BAL)
corresponds exactly
=
AMP
Bound ligand (Het Group name = AMP)
corresponds exactly
+ diphosphate
+ (R)-pantothenate
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     pantothenate biosynthetic process   1 term 
  Biochemical function     nucleotide binding     5 terms  

 

 
    reference    
 
 
DOI no: 10.1021/bi051873e Biochemistry 45:1554-1561 (2006)
PubMed id: 16460002  
 
 
Crystal structure of the pantothenate synthetase from Mycobacterium tuberculosis, snapshots of the enzyme in action.
S.Wang, D.Eisenberg.
 
  ABSTRACT  
 
Pantothenate synthetase (PS) from Mycobacterium tuberculosis represents a potential target for antituberculosis drugs. PS catalyzes the ATP-dependent condensation of pantoate and beta-alanine to form pantothenate. Previously, we determined the crystal structure of PS from M. tuberculosis and its complexes with AMPCPP, pantoate, and pantoyl adenylate. Here, we describe the crystal structure of this enzyme complexed with AMP and its last substrate, beta-alanine, and show that the phosphate group of AMP serves as an anchor for the binding of beta-alanine. This structure confirms that binding of beta-alanine in the active site cavity can occur only after formation of the pantoyl adenylate intermediate. A new crystal form was also obtained; it displays the flexible wall of the active site cavity in a conformation incapable of binding pantoate. Soaking of this crystal form with ATP and pantoate gives a fully occupied complex of PS with ATP. Crystal structures of these complexes with substrates, the reaction intermediate, and the reaction product AMP provide a step-by-step view of the PS-catalyzed reaction. A detailed reaction mechanism and its implications for inhibitor design are discussed.
 

Literature references that cite this PDB file's key reference

  PubMed id Reference
20440844 A.X.Song, C.J.Zhou, X.Guan, K.H.Sze, and H.Y.Hu (2010).
Solution structure of the N-terminal domain of DC-UbP/UBTD2 and its interaction with ubiquitin.
  Protein Sci, 19, 1104-1109.
PDB code: 2ksn
20059543 K.S.Chakrabarti, K.G.Thakur, B.Gopal, and S.P.Sarma (2010).
X-ray crystallographic and NMR studies of pantothenate synthetase provide insights into the mechanism of homotropic inhibition by pantoate.
  FEBS J, 277, 697-712.
PDB code: 3guz
19714201 O.C.Redfern, B.H.Dessailly, T.J.Dallman, I.Sillitoe, and C.A.Orengo (2009).
FLORA: a novel method to predict protein function from structure in diverse superfamilies.
  PLoS Comput Biol, 5, e1000485.  
19481971 T.R.Ioerger, and J.C.Sacchettini (2009).
Structural genomics approach to drug discovery for Mycobacterium tuberculosis.
  Curr Opin Microbiol, 12, 318-325.  
18821554 A.Ciulli, D.E.Scott, M.Ando, F.Reyes, S.A.Saldanha, K.L.Tuck, D.Y.Chirgadze, T.L.Blundell, and C.Abell (2008).
Inhibition of Mycobacterium tuberculosis pantothenate synthetase by analogues of the reaction intermediate.
  Chembiochem, 9, 2606-2611.
PDB codes: 3cov 3cow 3coy 3coz
18422645 S.Ronconi, R.Jonczyk, and U.Genschel (2008).
A novel isoform of pantothenate synthetase in the Archaea.
  FEBS J, 275, 2754-2764.  
  17554169 J.Seetharamappa, M.Oke, H.Liu, S.A.McMahon, K.A.Johnson, L.Carter, M.Dorward, M.Zawadzki, I.M.Overton, C.A.van Niekirk, S.Graham, C.H.Botting, G.L.Taylor, M.F.White, G.J.Barton, P.J.Coote, and J.H.Naismith (2007).
Purification, crystallization and data collection of methicillin-resistant Staphylococcus aureus Sar2676, a pantothenate synthetase.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 488-491.  
16990935 K.L.Tuck, S.A.Saldanha, L.M.Birch, A.G.Smith, and C.Abell (2006).
The design and synthesis of inhibitors of pantothenate synthetase.
  Org Biomol Chem, 4, 3598-3610.  
17040917 R.Jonczyk, and U.Genschel (2006).
Molecular adaptation and allostery in plant pantothenate synthetases.
  J Biol Chem, 281, 37435-37446.  
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 code is shown on the right.