PDBsum entry 1lbf

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Lyase PDB id
Protein chain
247 a.a. *
Waters ×253
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Crystal structure of indole-3-glycerol phosphate syntase (igps)with reduced 1-(o-caboxyphenylamino)-1-deoxyribulose 5-phosphate (rcdrp)
Structure: Indole-3-glycerol phosphate synthase. Chain: a. Engineered: yes
Source: Sulfolobus solfataricus. Organism_taxid: 2287. Expressed in: escherichia coli. Expression_system_taxid: 562
2.05Å     R-factor:   0.152     R-free:   0.225
Authors: M.Hennig,B.Darimont,K.Kirschner,J.N.Jansonius
Key ref:
M.Hennig et al. (2002). The catalytic mechanism of indole-3-glycerol phosphate synthase: crystal structures of complexes of the enzyme from Sulfolobus solfataricus with substrate analogue, substrate, and product. J Mol Biol, 319, 757-766. PubMed id: 12054868 DOI: 10.1016/S0022-2836(02)00378-9
03-Apr-02     Release date:   12-Jun-02    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q06121  (TRPC_SULSO) -  Indole-3-glycerol phosphate synthase
248 a.a.
247 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Indole-3-glycerol-phosphate synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Tryptophan Biosynthesis
      Reaction: 1-(2-carboxyphenylamino)-1-deoxy-D-ribulose 5-phosphate = 1-C- (3-indolyl)-glycerol 3-phosphate + CO2 + H2O
1-(2-carboxyphenylamino)-1-deoxy-D-ribulose 5-phosphate
Bound ligand (Het Group name = 137)
corresponds exactly
= 1-C- (3-indolyl)-glycerol 3-phosphate
+ CO(2)
+ H(2)O
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     metabolic process   5 terms 
  Biochemical function     catalytic activity     4 terms  


    Added reference    
DOI no: 10.1016/S0022-2836(02)00378-9 J Mol Biol 319:757-766 (2002)
PubMed id: 12054868  
The catalytic mechanism of indole-3-glycerol phosphate synthase: crystal structures of complexes of the enzyme from Sulfolobus solfataricus with substrate analogue, substrate, and product.
M.Hennig, B.D.Darimont, J.N.Jansonius, K.Kirschner.
Indoleglycerol phosphate synthase catalyzes the ring closure of an N-alkylated anthranilate to a 3-alkyl indole derivative, a reaction requiring Lewis acid catalysis in vitro. Here, we investigated the enzymatic reaction mechanism through X-ray crystallography of complexes of the hyperthermostable enzyme from Sulfolobus solfataricus with the substrate 1-(o-carboxyphenylamino) 1-deoxyribulose 5-phosphate, a substrate analogue and the product indole-3-glycerol phosphate. The substrate and the substrate analogue are bound to the active site in a similar, extended conformation between the previously identified phosphate binding site and a hydrophobic pocket for the anthranilate moiety. This binding mode is unproductive, because the carbon atoms that are to be joined are too far apart. The indole ring of the bound product resides in a second hydrophobic pocket adjacent to that of the anthranilate moiety of the substrate. Although the hydrophobic moiety of the substrate moves during catalysis from one hydrophobic pocket to the other, the triosephosphate moiety remains rigidly bound to the same set of hydrogen-bonding residues. Simultaneously, the catalytically important residues Lys53, Lys110 and Glu159 maintain favourable distances to the atoms of the ligand undergoing covalent changes. On the basis of these data, the structures of two putative catalytic intermediates were modelled into the active site. This new structural information and the modelling studies provide further insight into the mechanism of enzyme-catalyzed indole synthesis. The charged epsilon-amino group of Lys110 is the general acid, and the carboxylate group of Glu159 is the general base. Lys53 guides the substrate undergoing conformational transitions during catalysis, by forming a salt-bridge to the carboxylate group of its anthranilate moiety.
  Selected figure(s)  
Figure 4.
Figure 4. Stereoview of the difference electron density of the ligands bound to sIGPS, as it appears in electron density omit maps. These were computed with phases resulting from refinement, in which the ligand was omitted. The ligands are shown in a ball-and-stick representation with carbon, oxygen, nitrogen and phosphorus coloured white, red, blue and magenta, respectively, (a) rCdRP on a 2.05 Å map, contoured at 4s. (b) IGP on a 2.0 Å map, contoured at 4s. (c) CdRP and IGP on a 2.4 Å map, contoured at 2.5s. The Figure was produced with MOLOC.[29.]
Figure 6.
Figure 6. The proposed roles of K53, K110 and E159 of sIGPS in catalyzing the conversion of CdRP to IGP. Hydrogen bond distances are given in Table 3. (*) Asymmetric carbon atoms generated transiently. The arrows show how the reactions are assisted by the indicated catalytic residues. See the text for details. (a) The substrate bound unproductively as observed in the sIGPS:CdRP complex ( Figure 3(c)), with C1-C2' DISTANCE=4.8 Å. (b) The intermediate I1 as in Figure 5(a). (c) The intermediate I2 as in Figure 5(b). (d) The sIGPS:IGP complex as in Figure 3(b).
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2002, 319, 757-766) copyright 2002.  
  Figures were selected by the author.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19032598 H.Shen, F.Wang, Y.Zhang, Q.Huang, S.Xu, H.Hu, J.Yue, and H.Wang (2009).
A novel inhibitor of indole-3-glycerol phosphate synthase with activity against multidrug-resistant Mycobacterium tuberculosis.
  FEBS J, 276, 144-154.  
19237570 J.Claren, C.Malisi, B.Höcker, and R.Sterner (2009).
Establishing wild-type levels of catalytic activity on natural and artificial (beta alpha)8-barrel protein scaffolds.
  Proc Natl Acad Sci U S A, 106, 3704-3709.
PDB code: 2w79
18975945 A.N.Alexandrova, D.Röthlisberger, D.Baker, and W.L.Jorgensen (2008).
Catalytic mechanism and performance of computationally designed enzymes for Kemp elimination.
  J Am Chem Soc, 130, 15907-15915.  
18410248 R.Das, and D.Baker (2008).
Macromolecular modeling with rosetta.
  Annu Rev Biochem, 77, 363-382.  
17359995 Z.Gu, J.A.Zitzewitz, and C.R.Matthews (2007).
Mapping the structure of folding cores in TIM barrel proteins by hydrogen exchange mass spectrometry: the roles of motif and sequence for the indole-3-glycerol phosphate synthase from Sulfolobus solfataricus.
  J Mol Biol, 368, 582-594.  
16214343 A.Gutteridge, and J.M.Thornton (2005).
Understanding nature's catalytic toolkit.
  Trends Biochem Sci, 30, 622-629.  
15452341 D.Mazumder-Shivakumar, and T.C.Bruice (2004).
Molecular dynamics studies of ground state and intermediate of the hyperthermophilic indole-3-glycerol phosphate synthase.
  Proc Natl Acad Sci U S A, 101, 14379-14384.  
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