Scientists from the University of Heidelberg and the ETH Zurich have found out how bacteria synthesise pyridoxal 5'-phosphate (PLP), the biologically active form of vitamin B6 (Marco Strohmeier, Thomas Raschle, Jacel Mazurkiewicz, Karsten Rippe, Irmgard Sinning, Teresa B. Fitzpatrrick and Ivo Tews: "Structure of a bacterial pyridoxal 5'-phosphate synthase complex", Proceedings of the National Academy of Sciences, U.S.A.)
Though vitamin B6 was only discovered as recently as the 1940s, its crucial importance was immediately apparent. The present assumption is that this vitamin is involved in more metabolic processes than any other nutrient. Vitamin B6 deficiencies in the human diet can lead to severe disorders. The complex vitamin is necessary for the functioning of the immune system and the nervous system and is crucial for physical and mental health. Normally, the approx. 1.5 mg required for these purposes is covered by our daily intake of food.
A research group at Heidelberg University's Centre for Biochemistry (BZH) has now elucidated the molecular machinery used by bacteria to synthesise pyridoxal 5'-phosphate (PLP), which is the biologically active form of vitamin B6. This was achieved in close cooperation with the ETH Zurich in the framework of the international VITBIOMAL consortium receiving EU funding for research on the vitamin B6 biosynthesis of the malaria pathogen Plasmodium falciparum. The aim of the consortium is to develop new approaches to malaria therapy (for more details go to http://www.hyg.uni-heidelberg.de/vitbiomal/).
Many organisms can synthesise vitamin B6, including various bacteria, plants and the malaria pathogen. The Zurich research group itself was involved in the recent first-time description of the general synthesis pathway. For a long time it was assumed that in all organisms PLP synthesis functions in the same way as it does in the intestinal bacterium E. coli, the model organism in microbiology. But the new data indicate that most organisms use an entirely different biosynthetic route for PLP synthesis, in which an enzyme complex draws upon C5 and C3 sugars using glutamine as a nitrogen source. The structure of this complex has now been determined.
To elucidate the atomic structure of the enzyme the scientists used x-ray crystallography. It became apparent that the synthesis of PLP requires an enormous multi-enzyme complex consisting of 24 proteins. Twelve PLP synthase subunits form a double ring made up of six subunits each. Another 12 enzymatic subunits bind to PLP synthase and supply it with ammonium derived from the amino acid glutamine. This produces a total of 12 independent dual enzymes that can synthesise PLP. Knowledge of the molecular structure is a crucial step towards a better understanding of vitamin B6 biosynthesis.
The VitBioMal consortium consists of five research groups from four different European countries, including two from Heidelberg. For more information go to http://www.hyg.uni-heidelberg.de/vitbiomal/ or contact PD Dr. Barbara Kappes, Department of Parasitology, Institute of Hygiene, Heidelberg University Hospital, Im Neuenheimer Feld 326, D-69120 Heidelberg, phone: 06221/561774, fax: 564643, e-mail: firstname.lastname@example.org
Please address any inquiries on enzymatic structure to
Dr. Ivo Tews,
Research group Prof. Dr. I. Sinnig.
Biochemistry Centre of the University of Heidelberg (BZH)
Im Neuenheimer Feld 328,
phone: 06221/544788, fax: 544790
mobile phone: 0160/8231880
Dr. Teresa Fitzpatrick
Institute of Plant Sciences
Inquiries from journalists should be addressed to
Dr. Michael Schwarz
Press Officer of the University of Heidelberg
phone: 06221/542310, fax: 54317