Vitamin B12 - A Methylgroup without a Job

Vitamin B12 - A Methylgroup without a Job ?
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A. Lyskowski , P. Butler , M. Ebert , Bernhard Kräutler , K. Gruber and Ch. Kratky
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Institut für Chemie, Karl-Franzens Universität, Heinrichstrasse 28, A-8010 Graz, Austria
Institute of Organic Chemistry, and Centre of Molecular Biosciences, University of Innsbruck, Austria
Norvitamin B12 derivatives are newly discovered cofactors of Sulfurospirillum multivorans
tetrachloroethene reductive dehalogenase. In comparison with vitamin B12, norvitamin B12 lacks the methyl
group attached to C176 in the nucleotide loop. This cofactor analog could act as a potential cofactor for
glutamate mutase from Clostridium cochlearium.
The current study aimed at verifying the structure of synthesized norvitamin B12 and at analyzing the
functional significance of structural differences to vitamin B12.
Crystals of norvitamin B12 were grown from aqueous acetone and the structure was determined at
0.85 Å resolution (Figure 1).
The resulting structure is very similar to that of vitamin B12 [1]. A slightly longer (Co–N)-bond from the
cobalt ion to the lower axial base in norvitamin B12 (2.047(5) Å compared to 2.011(10) Å), a small increase
of the base tilt angle (the difference of the angles Co–N3N–C9N and Co–N3N–C2N) of 11.6(0.6)°
(compared to 9.7(1.1)°) and a small decrease in the corrin fold angle from 18.0(0.3)° to 15.8(0.1)° are all
consistent with a rather similar mechanochemical and steric effect of the nucleotide function [2].
Minor differences between the two structures were seen only in the region around the ethanolamine linker,
the phosphate and ribose moieties of the nucleotide loop. With the exception of the orientation of the amide
group of side chain a, even the conformations of the amide side chains were virtually identical.
Figure 1:Crystal structure of norvitamin B12, ball and stick model with C, N, O, P, Co atoms colored grey,
blue, red, green and pink, respectively.
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Figure 2: Superposition of models of the 3D-structures of 1 (red) and of vitamin B12 (yellow, C176 methyl
labeled green).
A manuscript on the structural results and a detailed chemical characterization has recently been
accepted for publication[3].
References
[1] B. Kräutler, R. Konrat, E. Stupperich, G. Färber, K. Gruber, C. Kratky, Inorg. Chem. 1994, 33,
4128-4139
[2] C. Kratky, B. Kräutler in Chemistry and Biochemistry of B12 (Ed.: R. Banerjee) John Wiley &
Sons, New York, 1999, pp. 9-41
[3] P. Butler, M.-O. Ebert, A. Lyskowski, K. Gruber, Ch. Kratky, B. Kräutler, Angew. Chem. Int. Ed.
Engl., in press
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