PDBsum entry 3d8t

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Lyase PDB id
Protein chains
252 a.a. *
ACT ×4
Waters ×598
* Residue conservation analysis
PDB id:
Name: Lyase
Title: Thermus thermophilus uroporphyrinogen iii synthase
Structure: Uroporphyrinogen-iii synthase. Chain: a, b. Engineered: yes
Source: Thermus thermophilus. Organism_taxid: 262724. Strain: hb27. Gene: tt_c0312. Expressed in: escherichia coli.
1.60Å     R-factor:   0.192     R-free:   0.236
Authors: H.L.Schubert
Key ref: H.L.Schubert et al. (2008). Structure and mechanistic implications of a uroporphyrinogen III synthase-product complex. Biochemistry, 47, 8648-8655. PubMed id: 18651750
23-May-08     Release date:   12-Aug-08    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
Q72KM1  (Q72KM1_THET2) -  Uroporphyrinogen-III synthase
253 a.a.
252 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - Uroporphyrinogen-III synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]

Porphyrin Biosynthesis (early stages)
      Reaction: Hydroxymethylbilane = uroporphyrinogen III + H2O
= uroporphyrinogen III
+ H(2)O
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     tetrapyrrole biosynthetic process   1 term 
  Biochemical function     lyase activity     2 terms  


    Added reference    
Biochemistry 47:8648-8655 (2008)
PubMed id: 18651750  
Structure and mechanistic implications of a uroporphyrinogen III synthase-product complex.
H.L.Schubert, J.D.Phillips, A.Heroux, C.P.Hill.
Uroporphyrinogen III synthase (U3S) catalyzes the asymmetrical cyclization of a linear tetrapyrrole to form the physiologically relevant uroporphyrinogen III (uro'gen III) isomer during heme biosynthesis. Here, we report four apoenzyme and one product complex crystal structures of the Thermus thermophilus (HB27) U3S protein. The overlay of eight crystallographically unique U3S molecules reveals a huge range of conformational flexibility, including a "closed" product complex. The product, uro'gen III, binds between the two domains and is held in place by a network of hydrogen bonds between the product's side chain carboxylates and the protein's main chain amides. Interactions of the product A and B ring carboxylate side chains with both structural domains of U3S appear to dictate the relative orientation of the domains in the closed enzyme conformation and likely remain intact during catalysis. The product C and D rings are less constrained in the structure, consistent with the conformational changes required for the catalytic cyclization with inversion of D ring orientation. A conserved tyrosine residue is potentially positioned to facilitate loss of a hydroxyl from the substrate to initiate the catalytic reaction.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20506125 G.Layer, J.Reichelt, D.Jahn, and D.W.Heinz (2010).
Structure and function of enzymes in heme biosynthesis.
  Protein Sci, 19, 1137-1161.  
20485863 S.Clavero, D.F.Bishop, U.Giger, M.E.Haskins, and R.J.Desnick (2010).
Feline congenital erythropoietic porphyria: two homozygous UROS missense mutations cause the enzyme deficiency and porphyrin accumulation.
  Mol Med, 16, 381-388.  
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