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PDBsum entry 1kzl

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protein ligands metals links
Transferase PDB id
1kzl
Jmol
Contents
Protein chain
202 a.a. *
Ligands
CRM ×2
Metals
_HG
Waters ×121
* Residue conservation analysis
PDB id:
1kzl
Name: Transferase
Title: Riboflavin synthase from s.Pombe bound to carboxyethyllumazine
Structure: Riboflavin synthase. Chain: a. Synonym: riboflavin synthase alpha chain. Engineered: yes
Source: Schizosaccharomyces pombe. Fission yeast. Organism_taxid: 4896. Expressed in: escherichia coli. Expression_system_taxid: 562.
Resolution:
2.10Å     R-factor:   0.185     R-free:   0.221
Authors: S.Gerhardt,A.K.Schott,N.Kairies,M.Cushman,B.Illarionov, W.Eisenreich,A.Bacher,R.Huber,S.Steinbacher,M.Fischer
Key ref:
S.Gerhardt et al. (2002). Studies on the reaction mechanism of riboflavin synthase: X-ray crystal structure of a complex with 6-carboxyethyl-7-oxo-8-ribityllumazine. Structure, 10, 1371-1381. PubMed id: 12377123 DOI: 10.1016/S0969-2126(02)00864-X
Date:
07-Feb-02     Release date:   06-Nov-02    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q9Y7P0  (RISA_SCHPO) -  Riboflavin synthase
Seq:
Struc:
208 a.a.
202 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 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
Bound ligand (Het Group name = CRM)
matches with 80.00% similarity
+ 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     nucleus   2 terms 
  Biological process     oxidation-reduction process   2 terms 
  Biochemical function     oxidoreductase activity     3 terms  

 

 
    Added reference    
 
 
DOI no: 10.1016/S0969-2126(02)00864-X Structure 10:1371-1381 (2002)
PubMed id: 12377123  
 
 
Studies on the reaction mechanism of riboflavin synthase: X-ray crystal structure of a complex with 6-carboxyethyl-7-oxo-8-ribityllumazine.
S.Gerhardt, A.K.Schott, N.Kairies, M.Cushman, B.Illarionov, W.Eisenreich, A.Bacher, R.Huber, S.Steinbacher, M.Fischer.
 
  ABSTRACT  
 
Riboflavin synthase catalyzes the disproportionation of 6,7-dimethyl-8-ribityllumazine affording riboflavin and 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione. We have determined the structure of riboflavin synthase from Schizosaccharomyces pombe in complex with the substrate analog, 6-carboxyethyl-7-oxo-8-ribityllumazine at 2.1 A resolution. In contrast to the homotrimeric solution state of native riboflavin synthase, we found the enzyme to be monomeric in the crystal structure. Structural comparison of the riboflavin synthases of S. pombe and Escherichia coli suggests oligomer contact sites and delineates the catalytic site for dimerization of the substrate and subsequent fragmentation of the pentacyclic intermediate. The pentacyclic substrate dimer was modeled into the proposed active site, and its stereochemical features were determined. The model suggests that the substrate molecule at the C-terminal domain donates a four-carbon unit to the substrate molecule bound at the N-terminal domain of an adjacent subunit in the oligomer.
 
  Selected figure(s)  
 
Figure 1.
Figure 1. Hypothetical Reaction Mechanism of Riboflavin Synthase1a, donor lumazine molecule; 1b, acceptor lumazine; X, proposed nucleophile, which neutralizes the carbonium centre at C-7 of 1b and enables carbanion attack at C-6 of 2 by the 7-exomethylene carbon of 1a [3 and 30]; R, ribityl chain.
 
  The above figure is reprinted by permission from Cell Press: Structure (2002, 10, 1371-1381) copyright 2002.  
  Figure was 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.  
20143812 R.R.Kim, B.Illarionov, M.Joshi, M.Cushman, C.Y.Lee, W.Eisenreich, M.Fischer, and A.Bacher (2010).
Mechanistic insights on riboflavin synthase inspired by selective binding of the 6,7-dimethyl-8-ribityllumazine exomethylene anion.
  J Am Chem Soc, 132, 2983-2990.  
19854891 Y.Sato, S.Shimizu, A.Ohtaki, K.Noguchi, H.Miyatake, N.Dohmae, S.Sasaki, M.Odaka, and M.Yohda (2010).
Crystal structures of the lumazine protein from Photobacterium kishitanii in complexes with the authentic chromophore, 6,7-dimethyl- 8-(1'-D-ribityl) lumazine, and its analogues, riboflavin and flavin mononucleotide, at high resolution.
  J Bacteriol, 192, 127-133.
PDB codes: 3a35 3a3b 3a3g
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.  
19117095 T.Y.Yu, R.D.O'Connor, A.C.Sivertsen, C.Chiauzzi, B.Poliks, M.Fischer, A.Bacher, I.Haase, M.Cushman, and J.Schaefer (2008).
(15)N{(31)P} REDOR NMR studies of the binding of phosphonate reaction intermediate analogues to Saccharomyces cerevisiae lumazine synthase.
  Biochemistry, 47, 13942-13951.  
18020947 B.Illarionov, W.Eisenreich, M.Wirth, C.Yong Lee, Y.Eun Woo, A.Bacher, and M.Fischer (2007).
Lumazine proteins from photobacteria: localization of the single ligand binding site to the N-terminal domain.
  Biol Chem, 388, 1313-1323.  
17898895 D.E.Scott, A.Ciulli, and C.Abell (2007).
Coenzyme biosynthesis: enzyme mechanism, structure and inhibition.
  Nat Prod Rep, 24, 1009-1026.  
17588214 F.Forouhar, A.Kuzin, J.Seetharaman, I.Lee, W.Zhou, M.Abashidze, Y.Chen, W.Yong, H.Janjua, Y.Fang, D.Wang, K.Cunningham, R.Xiao, T.B.Acton, E.Pichersky, D.F.Klessig, C.W.Porter, G.T.Montelione, and L.Tong (2007).
Functional insights from structural genomics.
  J Struct Funct Genomics, 8, 37-44.
PDB codes: 1rty 1sqs 1tm0 1zbp 2hd3 2nv4 2oys
17657909 J.Klages, M.Coles, and H.Kessler (2007).
NMR-based screening: a powerful tool in fragment-based drug discovery.
  Analyst, 132, 693-705.  
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.  
16607521 M.Mack, and S.Grill (2006).
Riboflavin analogs and inhibitors of riboflavin biosynthesis.
  Appl Microbiol Biotechnol, 71, 265-275.  
15843156 B.Illarionov, I.Haase, M.Fischer, A.Bacher, and N.Schramek (2005).
Pre-steady-state kinetic analysis of riboflavin synthase using a pentacyclic reaction intermediate as substrate.
  Biol Chem, 386, 127-136.  
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.  
15927885 M.Fischer, I.Haase, R.Feicht, N.Schramek, P.Köhler, P.Schieberle, and A.Bacher (2005).
Evolution of vitamin B2 biosynthesis: riboflavin synthase of Arabidopsis thaliana and its inhibition by riboflavin.
  Biol Chem, 386, 417-428.  
15208317 M.Fischer, W.Römisch, S.Saller, B.Illarionov, G.Richter, F.Rohdich, W.Eisenreich, and A.Bacher (2004).
Evolution of vitamin B2 biosynthesis: structural and functional similarity between pyrimidine deaminases of eubacterial and plant origin.
  J Biol Chem, 279, 36299-36308.  
14504292 B.Illarionov, I.Haase, A.Bacher, M.Fischer, and N.Schramek (2003).
Presteady state kinetic analysis of riboflavin synthase.
  J Biol Chem, 278, 47700-47706.  
14690539 M.Fischer, A.K.Schott, K.Kemter, R.Feicht, G.Richter, B.Illarionov, W.Eisenreich, S.Gerhardt, M.Cushman, S.Steinbacher, R.Huber, and A.Bacher (2003).
Riboflavin synthase of Schizosaccharomyces pombe. Protein dynamics revealed by 19F NMR protein perturbation experiments.
  BMC Biochem, 4, 18.  
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.