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Transferase PDB id
1kz9
Jmol
Contents
Protein chains
147 a.a. *
Ligands
PO4 ×5
Waters ×66
* Residue conservation analysis
PDB id:
1kz9
Name: Transferase
Title: Mutant enzyme l119f lumazine synthase from s.Pombe
Structure: 6,7-dimethyl-8-ribityllumazine synthase. Chain: a, b, c, d, e. Engineered: yes. Mutation: yes
Source: Schizosaccharomyces pombe. Fission yeast. Organism_taxid: 4896. Expressed in: escherichia coli. Expression_system_taxid: 562.
Biol. unit: Pentamer (from PQS)
Resolution:
3.10Å     R-factor:   0.194     R-free:   0.231
Authors: S.Gerhardt,I.Haase,S.Steinbacher,J.T.Kaiser,M.Cushman, A.Bacher,R.Huber,M.Fischer
Key ref:
S.Gerhardt et al. (2002). The structural basis of riboflavin binding to Schizosaccharomyces pombe 6,7-dimethyl-8-ribityllumazine synthase. J Mol Biol, 318, 1317-1329. PubMed id: 12083520 DOI: 10.1016/S0022-2836(02)00116-X
Date:
06-Feb-02     Release date:   24-Jul-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chains
Pfam   ArchSchema ?
Q9UUB1  (RIB4_SCHPO) -  6,7-dimethyl-8-ribityllumazine synthase
Seq:
Struc: 		159 a.a.
147 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Enzyme reactions 
   Enzyme class: E.C.2.5.1.9  - Riboflavin synthase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: 2 6,7-dimethyl-8-(1-D-ribityl)lumazine = riboflavin + 4-(1-D- ribitylamino)-5-amino-2,6-dihydroxypyrimidine
2 × 6,7-dimethyl-8-(1-D-ribityl)lumazine
 = riboflavin
 + 4-(1-D- ribitylamino)-5-amino-2,6-dihydroxypyrimidine
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     riboflavin synthase complex   3 terms 
  Biological process     riboflavin biosynthetic process   1 term 
  Biochemical function     transferase activity     2 terms  

 

 
    Added reference    
 
 
DOI no: 10.1016/S0022-2836(02)00116-X J Mol Biol 318:1317-1329 (2002)
PubMed id: 12083520  
 
 
The structural basis of riboflavin binding to Schizosaccharomyces pombe 6,7-dimethyl-8-ribityllumazine synthase.
S.Gerhardt, I.Haase, S.Steinbacher, J.T.Kaiser, M.Cushman, A.Bacher, R.Huber, M.Fischer.
 
  ABSTRACT  
 
Riboflavin is an essential cofactor in all organisms. Its direct biosynthetic precursor, 6,7-dimethyl-8-ribityllumazine, is synthesised by the enzyme 6,7-dimethyl-8-ribityllumazine synthase. Recently, we have found that the enzyme from Schizosaccharomyces pombe binds riboflavin, the final product of the pathway with a relatively high affinity with a KD of 1.2 microM. Here, we report on the crystal structure of lumazine synthase from S. pombe with bound riboflavin and compare the binding mode with those of the substrate analogue inhibitor 5-nitro-6-(D-ribitylamino)-2,4(1H,3H)-pyrimidinedione and of the product analogue 6-carboxyethyl-7-oxo-8-ribityllumazine. In all complexes the pyrimidinedione moieties of each respective ligand bind in a very similar orientation. Binding of riboflavin additionally involves a stacking interaction of the dimethylbenzene moiety with the side-chain of His94, a highly conserved residue in all lumazine synthases. The enzyme from Bacillus subtilis showed a KD of at least 1 mM whereas the very homologous enzyme from Saccharomyces cerevisiae had a comparable KD of 3.9 microM. Structural comparison of the S. cerevisiae, the S. pombe, and the mutant enzymes suggests that fine tuning of affinity is achieved by influencing this stacking interaction.
 
  Selected figure(s)  
 
Figure 5.
Figure 5. Pentameric assembly of S. pombe lumazine synthase viewed along the 5-fold non-crystallographic symmetry axis. The active sites are built up by two adjacent monomers. Bound riboflavin is shown in ball-and-stick. 		Figure 9.
Figure 9. Stereo view of superposition of the active site residues formed by two adjacent monomers of the yeast lumazine synthases from S. pombe (red) and S. cerevisiae[16] (blue). Bound riboflavin (yellow) in case of the S. pombe enzyme is in almost the same position as the bound inhibitor 5-(6- Image -ribitylamino-2,4-dihydroxypyrimidine-5-yl)-1-pentyl-phosphonic acid (green) in case of S. cerevisiae. Numbers refer to amino acid residues from S. pombe lumazine synthase.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (2002, 318, 1317-1329) copyright 2002.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21404408 M.Fischer, and A.Bacher (2011).
Biosynthesis of vitamin B2: a unique way to assemble a xylene ring.
  Chembiochem, 12, 670-680.  
20430628 A.Talukdar, E.Morgunova, J.Duan, W.Meining, N.Foloppe, L.Nilsson, A.Bacher, B.Illarionov, M.Fischer, R.Ladenstein, and M.Cushman (2010).
Virtual screening, selection and development of a benzindolone structural scaffold for inhibition of lumazine synthase.
  Bioorg Med Chem, 18, 3518-3534.  
20823551 E.Morgunova, B.Illarionov, S.Saller, A.Popov, T.Sambaiah, A.Bacher, M.Cushman, M.Fischer, and R.Ladenstein (2010).
Structural study and thermodynamic characterization of inhibitor binding to lumazine synthase from Bacillus anthracis.
  Acta Crystallogr D Biol Crystallogr, 66, 1001-1011.
PDB codes: 1vsw 1vsx 3jv8
19552377 A.Talukdar, M.Breen, A.Bacher, B.Illarionov, M.Fischer, G.Georg, Q.Z.Ye, and M.Cushman (2009).
Discovery and development of a small molecule library with lumazine synthase inhibitory activity.
  J Org Chem, 74, 5123-5134.  
19224924 M.Grininger, H.Staudt, P.Johansson, J.Wachtveitl, and D.Oesterhelt (2009).
Dodecin is the key player in flavin homeostasis of archaea.
  J Biol Chem, 284, 13068-13076.
PDB codes: 2vx9 2vxa
  18607092 L.Rodríguez-Fernández, F.J.López-Jaramillo, A.Bacher, M.Fischer, and S.Weinkauf (2008).
Improvement of the quality of lumazine synthase crystals by protein engineering.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 64, 625-628.  
17446177 E.Morgunova, S.Saller, I.Haase, M.Cushman, A.Bacher, M.Fischer, and R.Ladenstein (2007).
Lumazine synthase from Candida albicans as an anti-fungal target enzyme: structural and biochemical basis for drug design.
  J Biol Chem, 282, 17231-17241.
PDB code: 2jfb
17289680 R.H.Duurkens, M.B.Tol, E.R.Geertsma, H.P.Permentier, and D.J.Slotboom (2007).
Flavin binding to the high affinity riboflavin transporter RibU.
  J Biol Chem, 282, 10380-10386.  
17348709 Y.Zhang, B.Illarionov, A.Bacher, M.Fischer, G.I.Georg, Q.Z.Ye, D.Vander Velde, P.E.Fanwick, Y.Song, and M.Cushman (2007).
A novel lumazine synthase inhibitor derived from oxidation of 1,3,6,8-tetrahydroxy-2,7-naphthyridine to a tetraazaperylenehexaone derivative.
  J Org Chem, 72, 2769-2776.  
16272154 A.Ramsperger, M.Augustin, A.K.Schott, S.Gerhardt, T.Krojer, W.Eisenreich, B.Illarionov, M.Cushman, A.Bacher, R.Huber, and M.Fischer (2006).
Crystal structure of an archaeal pentameric riboflavin synthase in complex with a substrate analog inhibitor: stereochemical implications.
  J Biol Chem, 281, 1224-1232.
PDB codes: 2b98 2b99
16984393 E.Morgunova, B.Illarionov, T.Sambaiah, I.Haase, A.Bacher, M.Cushman, M.Fischer, and R.Ladenstein (2006).
Structural and thermodynamic insights into the binding mode of five novel inhibitors of lumazine synthase from Mycobacterium tuberculosis.
  FEBS J, 273, 4790-4804.
PDB codes: 2c92 2c94 2c97 2c9b 2c9d
16641488 K.J.Woycechowsky, F.P.Seebeck, and D.Hilvert (2006).
Tunnel plasticity and quaternary structural integrity of a pentameric protein ring.
  Protein Sci, 15, 1106-1114.  
16607521 M.Mack, and S.Grill (2006).
Riboflavin analogs and inhibitors of riboflavin biosynthesis.
  Appl Microbiol Biotechnol, 71, 265-275.  
16923880 V.Zylberman, S.Klinke, I.Haase, A.Bacher, M.Fischer, and F.A.Goldbaum (2006).
Evolution of vitamin B2 biosynthesis: 6,7-dimethyl-8-ribityllumazine synthases of Brucella.
  J Bacteriol, 188, 6135-6142.  
15944152 B.Illarionov, W.Eisenreich, N.Schramek, A.Bacher, and M.Fischer (2005).
Biosynthesis of vitamin B2: diastereomeric reaction intermediates of archaeal and non-archaeal riboflavin synthases.
  J Biol Chem, 280, 28541-28546.  
16277343 M.Cushman, G.Jin, T.Sambaiah, B.Illarionov, M.Fischer, R.Ladenstein, and A.Bacher (2005).
Design, synthesis, and biochemical evaluation of 1,5,6,7-tetrahydro-6,7-dioxo-9-D-ribitylaminolumazines bearing alkyl phosphate substituents as inhibitors of lumazine synthase and riboflavin synthase.
  J Org Chem, 70, 8162-8170.  
16010344 M.Fischer, and A.Bacher (2005).
Biosynthesis of flavocoenzymes.
  Nat Prod Rep, 22, 324-350.  
15265040 M.Koch, C.Breithaupt, S.GerhardtHaase, S.Weber, M.Cushman, R.Huber, A.Bacher, and M.Fischer (2004).
Structural basis of charge transfer complex formation by riboflavin bound to 6,7-dimethyl-8-ribityllumazine synthase.
  Eur J Biochem, 271, 3208-3214.
PDB codes: 2a57 2a58 2a59
14660615 V.Zylberman, P.O.Craig, S.Klinke, B.C.Braden, A.Cauerhff, and F.A.Goldbaum (2004).
High order quaternary arrangement confers increased structural stability to Brucella sp. lumazine synthase.
  J Biol Chem, 279, 8093-8101.  
12603336 I.Haase, S.Mörtl, P.Köhler, A.Bacher, and M.Fischer (2003).
Biosynthesis of riboflavin in archaea. 6,7-dimethyl-8-ribityllumazine synthase of Methanococcus jannaschii.
  Eur J Biochem, 270, 1025-1032.  
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.