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Structural insights into the catalytic mechanism of the yeast pyridoxal 5-phosphate synthase Snz1.

Zhang X, Teng YB, Liu JP, He YX, Zhou K, Chen Y, Zhou CZ
Biochem J 432 445-50 (2010)
Related entries: 3o05, 3o06

Cited: 16 times
EuropePMC logo PMID: 20919991

Abstract

In most eubacteria, fungi, apicomplexa, plants and some metazoans, the active form of vitamin B6, PLP (pyridoxal 5-phosphate), is de novo synthesized from three substrates, R5P (ribose 5-phosphate), DHAP (dihydroxyacetone phosphate) and ammonia hydrolysed from glutamine by a complexed glutaminase. Of the three active sites of DXP (deoxyxylulose 5-phosphate)independent PLP synthase (Pdx1), the R5P isomerization site has been assigned, but the sites for DHAP isomerization and PLP formation remain unknown. In the present study, we present the crystal structures of yeast Pdx1/Snz1, in apo-, G3P (glyceraldehyde 3-phosphate)- and PLP-bound forms, at 2.3, 1.8 and 2.2 Å (1 Å=0.1 nm) respectively. Structural and biochemical analysis enabled us to assign the PLP-formation site, a G3P-binding site and a G3P-transfer site. We propose a putative catalytic mechanism for Pdx1/Snz1 in which R5P and DHAP are isomerized at two distinct sites and transferred along well-defined routes to a final destination for PLP synthesis.

Articles - 3o07 mentioned but not cited (3)

  1. Structural definition of the lysine swing in Arabidopsis thaliana PDX1: Intermediate channeling facilitating vitamin B6 biosynthesis. Robinson GC, Kaufmann M, Roux C, Fitzpatrick TB. Proc Natl Acad Sci U S A 113 E5821-E5829 (2016)
  2. Tunable Heteroassembly of a Plant Pseudoenzyme-Enzyme Complex. Novikova IV, Zhou M, Du C, Parra M, Kim DN, VanAernum ZL, Shaw JB, Hellmann H, Wysocki VH, Evans JE. ACS Chem Biol 16 2315-2325 (2021)
  3. Overexpression, crystallization and preliminary X-ray crystallographic analysis of pyridoxal biosynthesis lyase PdxS from Pyrococcus horikoshii. Yoon JY, Park CR, Lee HH, Suh SW. Acta Crystallogr Sect F Struct Biol Cryst Commun 68 440-442 (2012)


Reviews citing this publication (3)

  1. Vitamin requirements and biosynthesis in Saccharomyces cerevisiae. Perli T, Wronska AK, Ortiz-Merino RA, Pronk JT, Daran JM. Yeast 37 283-304 (2020)
  2. Vitamin Biosynthesis as an Antifungal Target. Meir Z, Osherov N. J Fungi (Basel) 4 E72 (2018)
  3. Structural Dynamics and Perspectives of Vitamin B6 Biosynthesis Enzymes in Plasmodium: Advances and Open Questions. Barra ALC, Ullah N, Morão LG, Wrenger C, Betzel C, Nascimento AS. Front Cell Infect Microbiol 11 688380 (2021)

Articles citing this publication (10)

  1. Assembly of the eukaryotic PLP-synthase complex from Plasmodium and activation of the Pdx1 enzyme. Guédez G, Hipp K, Windeisen V, Derrer B, Gengenbacher M, Böttcher B, Sinning I, Kappes B, Tews I. Structure 20 172-184 (2012)
  2. Engineering a pyridoxal 5'-phosphate supply for cadaverine production by using Escherichia coli whole-cell biocatalysis. Ma W, Cao W, Zhang B, Chen K, Liu Q, Li Y, Ouyang P. Sci Rep 5 15630 (2015)
  3. Crystal structures capture three states in the catalytic cycle of a pyridoxal phosphate (PLP) synthase. Smith AM, Brown WC, Harms E, Smith JL. J Biol Chem 290 5226-5239 (2015)
  4. Improvement of whole-cell transamination with Saccharomyces cerevisiae using metabolic engineering and cell pre-adaptation. Weber N, Gorwa-Grauslund M, Carlquist M. Microb Cell Fact 16 3 (2017)
  5. Lysine relay mechanism coordinates intermediate transfer in vitamin B6 biosynthesis. Rodrigues MJ, Windeisen V, Zhang Y, Guédez G, Weber S, Strohmeier M, Hanes JW, Royant A, Evans G, Sinning I, Ealick SE, Begley TP, Tews I. Nat Chem Biol 13 290-294 (2017)
  6. Crystal structure of pyridoxal biosynthesis lyase PdxS from Pyrococcus horikoshii. Matsuura A, Yoon JY, Yoon HJ, Lee HH, Suh SW. Mol Cells 34 407-412 (2012)
  7. Exploring inhibition of Pdx1, a component of the PLP synthase complex of the human malaria parasite Plasmodium falciparum. Reeksting SB, Müller IB, Burger PB, Burgos ES, Salmon L, Louw AI, Birkholtz LM, Wrenger C. Biochem J 449 175-187 (2013)
  8. Enhancing the production of γ-aminobutyric acid in Escherichia coli BL21 by engineering the enzymes of the regeneration pathway of the coenzyme factor pyridoxal 5'-phosphate. Yu P, Ma J, Zhu P, Chen Q, Zhang Q. World J Microbiol Biotechnol 37 130 (2021)
  9. Recombinant Expression, Purification and Characterization of Pyridoxal 5'-phosphate Synthase from Geobacillus sp. H6a, Thermophilic Bacterium Producing Extracellular Vitamin B6. Sinthusiri A, Champasri C, Trongpanich Y. Iran J Biotechnol 19 e2575 (2021)
  10. Trapping and structural characterisation of a covalent intermediate in vitamin B6 biosynthesis catalysed by the Pdx1 PLP synthase. Rodrigues MJ, Giri N, Royant A, Zhang Y, Bolton R, Evans G, Ealick SE, Begley T, Tews I. RSC Chem Biol 3 227-230 (2022)


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