PDBsum entry 4n7b

Oxidoreductase

PDB id: 4n7b

Contents

Protein chain

318 a.a.

Ligands

F3S

SO4 ×2

GOL

Metals

_NA ×2

Waters ×189

PDB id:

4n7b

Name:

Oxidoreductase

Title:

Structure of the e-1-hydroxy-2-methyl-but-2-enyl-4-diphosphate reductase from plasmodium falciparum

Structure:

Lytb. Chain: a. Engineered: yes

Source:

Plasmodium falciparum. Organism_taxid: 5833. Gene: lytb. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.20Å R-factor: 0.173 R-free: 0.195

Authors:

I.Rekittke,H.Jomaa,U.Ermler

Key ref:

I.Rekittke et al. (2013). Structure of the (E)-4-hydroxy-3-methyl-but-2-enyl-diphosphate reductase from Plasmodium falciparum. Febs Lett, 587, 3968-3972. PubMed id: 24188825 DOI: 10.1016/j.febslet.2013.10.029

Date:

15-Oct-13 Release date: 20-Nov-13

Protein chain

Q8I295  (Q8I295_PLAF7) -  4-hydroxy-3-methylbut-2-enyl diphosphate reductase, apicoplast from Plasmodium falciparum (isolate 3D7)

Seq: 535 a.a.

Struc: 318 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.1.17.7.4 - 4-hydroxy-3-methylbut-2-enyl diphosphate reductase.
• Reaction:
  1. isopentenyl diphosphate + 2 oxidized [2Fe-2S]-[ferredoxin] + H2O = (2E)-4-hydroxy-3-methylbut-2-enyl diphosphate + 2 reduced [2Fe-2S]- [ferredoxin] + 2 H⁺
  2. dimethylallyl diphosphate + 2 oxidized [2Fe-2S]-[ferredoxin] + H2O = (2E)-4-hydroxy-3-methylbut-2-enyl diphosphate + 2 reduced [2Fe-2S]- [ferredoxin] + 2 H⁺
• Cofactor: Iron-sulfur

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

reference

DOI no: 10.1016/j.febslet.2013.10.029

Febs Lett 587:3968-3972 (2013)

PubMed id: 24188825

Structure of the (E)-4-hydroxy-3-methyl-but-2-enyl-diphosphate reductase from Plasmodium falciparum.

I.Rekittke, E.Olkhova, J.Wiesner, U.Demmer, E.Warkentin, H.Jomaa, U.Ermler.

ABSTRACT

Terpenoid precursor biosynthesis occurs in human and many pathogenic organisms via the mevalonate and 2-C-methyl-d-erythritol-4-phosphate (MEP) pathways, respectively. We determined the X-ray structure of the Fe/S containing (E)-4-hydroxy-3-methyl-but-2-enyl-diphosphate reductase (LytB) of the pathogenic protozoa Plasmodium falciparum which catalyzes the terminal step of the MEP pathway. The cloverleaf fold and the active site of P. falciparum LytB corresponds to those of the Aquifex aeolicus and Escherichia coli enzymes. Its distinct electron donor [2Fe-2S] ferredoxin was modeled to its binding site by docking calculations. The presented structural data provide a platform for a rational search of anti-malarian drugs.