The TMR B12 Network
A Collaborative Project Across Europe
email : firstname.lastname@example.org
(United Kingdom), Marburg (Germany), Karlsruhe
(Germany), Bern (Switzerland),
Innsbruck (Austria), Graz
(Austria), Ulm (Germany), Budapest
5th European Symposium
B12 and B12-Proteins
will be held in Marburg
- 15th September,
Also, a related meeting:
in Enzymatic Catalysis
will be held in Marburg
- 14th April, 2000
The last network meeting was held in Graz
on November 27th -28th with a
crystallography workshop November 29th - December 1st
meeting was held 18th-20th of June 1999.
B12 Toolbox was held in Marburg the 5th-9th of May 1999.
Objectives of the Network:
The network aims to define with atomic precision the discrete
steps occurring at the active sites of enzymes dependent on coenzyme forms
of vitamin B12. These enzymes catalyse an array of reactions
important for both prokaryotic and eukaryotic organisms, including humans.
The research programme will enable sufficient of the individual enzymes
to be isolated for structural analyses by X-ray and spectroscopic methods.
The hypothesis ('fragmentation-recombination mechanism') that emerged from
a previous programme requires verification. To this end, electron paramagnetic
resonance spectroscopy will be used to probe the nature of protein-bound,
intermediate free radicals and to search for radical centres that may be
located on the protein. In parallel with the enzymic studies, modified
and isotopically labelled coenzymes will be used to probe enzyme-coenzyme
interactions, and especially the mode of activation of the coenzyme for
the initiation of reactions: homolytic Co-C bond cleavage for the coenzyme
called adenosylcobalamin, heterolytic cleavage for the coenzyme methylcobalamin.
Model studies will attempt to replicate all of the main features of the
reaction pathways accomplished by the B12-dependent enzymes.
Results and Achievements:
to Group Research Pages
The crystal structure of the enzyme glutamate mutase from
Clostridium cochlearium has been elucidated (Graz and Marburg) and
shows clearly the mode of substrate binding.
The solution structure of component S of glutamate mutase
from Clostridium cochlearium has been determined by NMR (Innsbruck
The substrate-derived radical (4-glutamyl, i.e. the key intermediate)
in the glutamate mutase reaction has been characterised by EPR (Marburg
New insights into reaction mechanisms based on ab initio
molecular orbital calculations of reaction pathways have been gained by
an international co-operation with Canberra (Newcastle).
Efficient model systems for methyltransferases have been
developed, e.g. activation of methanol using cob(I)alamin (Bern).
Routine gene technological methods for obtaining recombinant
coenzyme B12-dependent enzymes have been developed (Karlsruhe,
Innsbruck, Marburg and Ulm).
Vitamin; enzyme; coenzyme; rearrangement; radical.
Last Updated 23rd February 1998