Structural highlights
Function
PDX2_PLAF7 Catalyzes the hydrolysis of glutamine to glutamate and ammonia as part of the biosynthesis of pyridoxal 5'-phosphate. The resulting ammonia molecule is channeled to the active site of Pdx1.[1] [2]
Publication Abstract from PubMed
Biosynthesis of vitamins is fundamental to malaria parasites. Plasmodia synthesize the active form of vitamin B(6) (pyridoxal 5'-phosphate, PLP) using a PLP synthase complex. The EM analysis shown here reveals a random association pattern of up to 12 Pdx2 glutaminase subunits to the dodecameric Pdx1 core complex. Interestingly, Plasmodium falciparum PLP synthase organizes in fibers. The crystal structure shows differences in complex formation to bacterial orthologs as interface variations. Alternative positioning of an alpha helix distinguishes an open conformation from a closed state when the enzyme binds substrate. The pentose substrate is covalently attached through its C1 and forms a Schiff base with Lys84. Ammonia transfer between Pdx2 glutaminase and Pdx1 active sites is regulated by a transient tunnel. The mutagenesis analysis allows defining the requirement for conservation of critical methionines, whereas there is also plasticity in ammonia tunnel construction as seen from comparison across different species.
Assembly of the Eukaryotic PLP-Synthase Complex from Plasmodium and Activation of the Pdx1 Enzyme.,Guedez G, Hipp K, Windeisen V, Derrer B, Gengenbacher M, Bottcher B, Sinning I, Kappes B, Tews I Structure. 2012 Jan 11;20(1):172-84. PMID:22244765[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Wrenger C, Eschbach ML, Müller IB, Warnecke D, Walter RD. Analysis of the vitamin B6 biosynthesis pathway in the human malaria parasite Plasmodium falciparum. J Biol Chem. 2005 Feb 18;280(7):5242-8. PMID:15590634 doi:10.1074/jbc.M412475200
- ↑ Gengenbacher M, Fitzpatrick TB, Raschle T, Flicker K, Sinning I, Muller S, Macheroux P, Tews I, Kappes B. Vitamin B6 biosynthesis by the malaria parasite Plasmodium falciparum: biochemical and structural insights. J Biol Chem. 2006 Feb 10;281(6):3633-41. Epub 2005 Dec 8. PMID:16339145 doi:10.1074/jbc.M508696200
- ↑ Guedez G, Hipp K, Windeisen V, Derrer B, Gengenbacher M, Bottcher B, Sinning I, Kappes B, Tews I. Assembly of the Eukaryotic PLP-Synthase Complex from Plasmodium and Activation of the Pdx1 Enzyme. Structure. 2012 Jan 11;20(1):172-84. PMID:22244765 doi:10.1016/j.str.2011.11.015
