4n7b

Structure of the E-1-hydroxy-2-methyl-but-2-enyl-4-diphosphate reductase from Plasmodium falciparumStructure of the E-1-hydroxy-2-methyl-but-2-enyl-4-diphosphate reductase from Plasmodium falciparum

Structural highlights

4n7b is a 1 chain structure with sequence from Plasmodium falciparum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	, , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ISPH_PLAF7 Catalyzes the conversion of 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate (HMBPP) into a mixture of isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). Acts in the terminal step of the DOXP/MEP pathway for isoprenoid precursor biosynthesis.^[1]

Publication Abstract from PubMed

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.

Structure of the (E)-4-hydroxy-3-methyl-but-2-enyl-diphosphate reductase from Plasmodium falciparum.,Rekittke I, Olkhova E, Wiesner J, Demmer U, Warkentin E, Jomaa H, Ermler U FEBS Lett. 2013 Nov 1. pii: S0014-5793(13)00799-0. doi:, 10.1016/j.febslet.2013.10.029. PMID:24188825^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Rohrich RC, Englert N, Troschke K, Reichenberg A, Hintz M, Seeber F, Balconi E, Aliverti A, Zanetti G, Kohler U, Pfeiffer M, Beck E, Jomaa H, Wiesner J. Reconstitution of an apicoplast-localised electron transfer pathway involved in the isoprenoid biosynthesis of Plasmodium falciparum. FEBS Lett. 2005 Nov 21;579(28):6433-8. doi: 10.1016/j.febslet.2005.10.037. Epub , 2005 Nov 2. PMID:16289098 doi:http://dx.doi.org/10.1016/j.febslet.2005.10.037
↑ Rekittke I, Olkhova E, Wiesner J, Demmer U, Warkentin E, Jomaa H, Ermler U. Structure of the (E)-4-hydroxy-3-methyl-but-2-enyl-diphosphate reductase from Plasmodium falciparum. FEBS Lett. 2013 Nov 1. pii: S0014-5793(13)00799-0. doi:, 10.1016/j.febslet.2013.10.029. PMID:24188825 doi:http://dx.doi.org/10.1016/j.febslet.2013.10.029

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OCA

[1] Rohrich RC, Englert N, Troschke K, Reichenberg A, Hintz M, Seeber F, Balconi E, Aliverti A, Zanetti G, Kohler U, Pfeiffer M, Beck E, Jomaa H, Wiesner J. Reconstitution of an apicoplast-localised electron transfer pathway involved in the isoprenoid biosynthesis of Plasmodium falciparum. FEBS Lett. 2005 Nov 21;579(28):6433-8. doi: 10.1016/j.febslet.2005.10.037. Epub , 2005 Nov 2. PMID:16289098 doi:http://dx.doi.org/10.1016/j.febslet.2005.10.037

[2] Rekittke I, Olkhova E, Wiesner J, Demmer U, Warkentin E, Jomaa H, Ermler U. Structure of the (E)-4-hydroxy-3-methyl-but-2-enyl-diphosphate reductase from Plasmodium falciparum. FEBS Lett. 2013 Nov 1. pii: S0014-5793(13)00799-0. doi:, 10.1016/j.febslet.2013.10.029. PMID:24188825 doi:http://dx.doi.org/10.1016/j.febslet.2013.10.029

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