The assembly of the plasmodial PLP synthase complex follows a defined course.

<h4>Background</h4>Plants, fungi, bacteria and the apicomplexan parasite Plasmodium falciparum are able to synthesize vitamin B6 de novo, whereas mammals depend upon the uptake of this essential nutrient from their diet. The active form of vitamin B6 is pyridoxal 5-phosphate (PLP). For i...

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Autores principales:	Ingrid B Müller, Julia Knöckel, Matthew R Groves, Rositsa Jordanova, Steven E Ealick, Rolf D Walter, Carsten Wrenger
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2008
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2b532528f125443a93abd033fd13f5a8
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spelling	oai:doaj.org-article:2b532528f125443a93abd033fd13f5a82021-11-25T06:13:03ZThe assembly of the plasmodial PLP synthase complex follows a defined course.1932-620310.1371/journal.pone.0001815https://doaj.org/article/2b532528f125443a93abd033fd13f5a82008-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/18350152/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Plants, fungi, bacteria and the apicomplexan parasite Plasmodium falciparum are able to synthesize vitamin B6 de novo, whereas mammals depend upon the uptake of this essential nutrient from their diet. The active form of vitamin B6 is pyridoxal 5-phosphate (PLP). For its synthesis two enzymes, Pdx1 and Pdx2, act together, forming a multimeric complex consisting of 12 Pdx1 and 12 Pdx2 protomers.<h4>Methodology/principal findings</h4>Here we report amino acid residues responsible for stabilization of the structural and enzymatic integrity of the plasmodial PLP synthase, identified by using distinct mutational analysis and biochemical approaches. Residues R85, H88 and E91 (RHE) are located at the Pdx1:Pdx1 interface and play an important role in Pdx1 complex assembly. Mutation of these residues to alanine impedes both Pdx1 activity and Pdx2 binding. Furthermore, changing D26, K83 and K151 (DKK), amino acids from the active site of Pdx1, to alanine obstructs not only enzyme activity but also formation of the complex. In contrast to the monomeric appearance of the RHE mutant, alteration of the DKK residues results in a hexameric assembly, and does not affect Pdx2 binding or its activity. While the modelled position of K151 is distal to the Pdx1:Pdx1 interface, it affects the assembly of hexameric Pdx1 into a functional dodecamer, which is crucial for PLP synthesis.<h4>Conclusions/significance</h4>Taken together, our data suggest that the assembly of a functional Pdx1:Pdx2 complex follows a defined pathway and that inhibition of this assembly results in an inactive holoenzyme.Ingrid B MüllerJulia KnöckelMatthew R GrovesRositsa JordanovaSteven E EalickRolf D WalterCarsten WrengerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 3, Iss 3, p e1815 (2008)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ingrid B Müller Julia Knöckel Matthew R Groves Rositsa Jordanova Steven E Ealick Rolf D Walter Carsten Wrenger The assembly of the plasmodial PLP synthase complex follows a defined course.
description	<h4>Background</h4>Plants, fungi, bacteria and the apicomplexan parasite Plasmodium falciparum are able to synthesize vitamin B6 de novo, whereas mammals depend upon the uptake of this essential nutrient from their diet. The active form of vitamin B6 is pyridoxal 5-phosphate (PLP). For its synthesis two enzymes, Pdx1 and Pdx2, act together, forming a multimeric complex consisting of 12 Pdx1 and 12 Pdx2 protomers.<h4>Methodology/principal findings</h4>Here we report amino acid residues responsible for stabilization of the structural and enzymatic integrity of the plasmodial PLP synthase, identified by using distinct mutational analysis and biochemical approaches. Residues R85, H88 and E91 (RHE) are located at the Pdx1:Pdx1 interface and play an important role in Pdx1 complex assembly. Mutation of these residues to alanine impedes both Pdx1 activity and Pdx2 binding. Furthermore, changing D26, K83 and K151 (DKK), amino acids from the active site of Pdx1, to alanine obstructs not only enzyme activity but also formation of the complex. In contrast to the monomeric appearance of the RHE mutant, alteration of the DKK residues results in a hexameric assembly, and does not affect Pdx2 binding or its activity. While the modelled position of K151 is distal to the Pdx1:Pdx1 interface, it affects the assembly of hexameric Pdx1 into a functional dodecamer, which is crucial for PLP synthesis.<h4>Conclusions/significance</h4>Taken together, our data suggest that the assembly of a functional Pdx1:Pdx2 complex follows a defined pathway and that inhibition of this assembly results in an inactive holoenzyme.
format	article
author	Ingrid B Müller Julia Knöckel Matthew R Groves Rositsa Jordanova Steven E Ealick Rolf D Walter Carsten Wrenger
author_facet	Ingrid B Müller Julia Knöckel Matthew R Groves Rositsa Jordanova Steven E Ealick Rolf D Walter Carsten Wrenger
author_sort	Ingrid B Müller
title	The assembly of the plasmodial PLP synthase complex follows a defined course.
title_short	The assembly of the plasmodial PLP synthase complex follows a defined course.
title_full	The assembly of the plasmodial PLP synthase complex follows a defined course.
title_fullStr	The assembly of the plasmodial PLP synthase complex follows a defined course.
title_full_unstemmed	The assembly of the plasmodial PLP synthase complex follows a defined course.
title_sort	assembly of the plasmodial plp synthase complex follows a defined course.
publisher	Public Library of Science (PLoS)
publishDate	2008
url	https://doaj.org/article/2b532528f125443a93abd033fd13f5a8
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The assembly of the plasmodial PLP synthase complex follows a defined course.

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