PDBsum entry 1nqw

Transferase

PDB id: 1nqw

Contents

Protein chains

154 a.a. *

Ligands

5YL ×5

Waters ×410

* Residue conservation analysis

PDB id:

1nqw

Name:

Transferase

Title:

Crystal structure of lumazine synthase from aquifex aeolicus in complex with inhibitor: 5-(6-d-ribitylamino-2,4(1h,3h) pyrimidinedione-5-yl)-1-pentyl-phosphonic acid

Structure:

6,7-dimethyl-8-ribityllumazine synthase. Chain: a, b, c, d, e. Synonym: dmrl synthase, lumazine synthase, riboflavin synthase beta chain. Engineered: yes

Source:

Aquifex aeolicus. Organism_taxid: 63363. Expressed in: escherichia coli. Expression_system_taxid: 562

Biol. unit:

60mer (from PDB file)

Resolution:

2.20Å R-factor: 0.161 R-free: 0.177

Authors:

X.Zhang,W.Meining,M.Cushman,I.Haase,M.Fischer,A.Bacher,R.Ladenstein

Key ref:

X.Zhang et al. (2003). A structure-based model of the reaction catalyzed by lumazine synthase from Aquifex aeolicus. J Mol Biol, 328, 167-182. PubMed id: 12684006 DOI: 10.1016/S0022-2836(03)00186-4

Date:

23-Jan-03 Release date: 23-Jan-04

Protein chains

O66529  (RISB_AQUAE) -  6,7-dimethyl-8-ribityllumazine synthase from Aquifex aeolicus (strain VF5)

Seq: 154 a.a.

Struc: 154 a.a.

Enzyme reactions

• Enzyme class: E.C.2.5.1.78 - 6,7-dimethyl-8-ribityllumazine synthase.
• Reaction: (2S)-2-hydroxy-3-oxobutyl phosphate + 5-amino-6-(D-ribitylamino)uracil = 6,7-dimethyl-8-(1-D-ribityl)lumazine + phosphate + 2 H2O + H⁺

(2S)-2-hydroxy-3-oxobutyl phosphate + 5-amino-6-(D-ribitylamino)uracil (Bound ligand (Het Group name = 5YL) matches with 64.29% similarity) = 6,7-dimethyl-8-(1-D-ribityl)lumazine + phosphate + 2 × H2O + H(+)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1016/S0022-2836(03)00186-4

J Mol Biol 328:167-182 (2003)

PubMed id: 12684006

A structure-based model of the reaction catalyzed by lumazine synthase from Aquifex aeolicus.

X.Zhang, W.Meining, M.Cushman, I.Haase, M.Fischer, A.Bacher, R.Ladenstein.

ABSTRACT

6,7-Dimethyl-8-ribityllumazine is the biosynthetic precursor of riboflavin, which, as a coenzyme, plays a vital role in the electron transfer process for energy production in all cellular organisms. The enzymes involved in lumazine biosynthesis have been studied in considerable detail. However, the conclusive mechanism of the reaction catalyzed by lumazine synthase has remained unclear. Here, we report four crystal structures of the enzyme from the hyperthermophilic bacterium Aquifex aeolicus in complex with different inhibitor compounds. The structures were refined at resolutions of 1.72 A, 1.85 A, 2.05 A and 2.2 A, respectively. The inhibitors have been designed in order to mimic the substrate, the putative reaction intermediates and the final product. Structural comparisons of the native enzyme and the inhibitor complexes as well as the kinetic data of single-site mutants of lumazine synthase from Bacillus subtilis showed that several highly conserved residues at the active site, namely Phe22, His88, Arg127, Lys135 and Glu138 are most likely involved in catalysis. A structural model of the catalytic process, which illustrates binding of substrates, enantiomer specificity, proton abstraction/donation, inorganic phosphate elimination, formation of the Schiff base and cyclization is proposed.

Selected figure(s)

Figure 3.
Figure 3. The 2F[o] -F[c] electron densitiy (s=1.5) around the active site of A. aeolicus lumazine synthase in complex with the product analogue 6,7-dioxo-5H-8-ribitylaminolumazine (RDL). The average B-factor of water molecules, indicated by red spheres, is below 21 Å2.

Figure 8.
Figure 8. Hypothetical mechanism for the biosynthesis of lumazine suggested by Kis et al.[12.]

The above figures are reprinted by permission from Elsevier: J Mol Biol (2003, 328, 167-182) copyright 2003.

Figures were selected by an automated process.