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Publication Abstract from PubMed

Coenzyme B(12)-dependent ethanolamine ammonia-lyase acts on both enantiomers of the substrate 2-amino-1-propanol [Diziol, P., et al. (1980) Eur. J. Biochem. 106, 211-224]. To rationalize this apparent lack of stereospecificity and the enantiomer-specific stereochemical courses of the deamination, we analyzed the X-ray structures of enantiomer-bound forms of the enzyme-cyanocobalamin complex. The lower affinity for the (R)-enantiomer may be due to the conformational change of the Valalpha326 side chain of the enzyme. In a manner consistent with the reported experimental results, we can predict that the pro-S hydrogen atom on C1 is abstracted by the adenosyl radical from both enantiomeric substrates, because it is the nearest one in both enantiomer-bound forms. We also predicted that the NH(2) group migrates from C2 to C1 by a suprafacial shift, with inversion of configuration at C1 for both enantiomeric substrates, although the absolute configuration of the 1-amino-1-propanol intermediate is not yet known. Reported labeling experiments demonstrate that (R)-2-amino-1-propanol is deaminated by the enzyme with inversion of configuration at C2, whereas the (S)-enantiomer is deaminated with retention. By taking these results into consideration, we can predict the rotameric radical intermediate from the (S)-enantiomer undergoes flipping to the rotamer from the (R)-enantiomer before the hydrogen back-abstraction. This suggests the preference of the enzyme active site for the rotamer from the (R)-enantiomer in equilibration. This preference might be explained in terms of the steric repulsion of the (S)-enantiomer-derived product radical at C3 with the Phealpha329 and Leualpha402 residues.

How coenzyme B12-dependent ethanolamine ammonia-lyase deals with both enantiomers of 2-amino-1-propanol as substrates: structure-based rationalization.,Shibata N, Higuchi Y, Toraya T Biochemistry. 2011 Feb 1;50(4):591-8. Epub 2010 Dec 30. PMID:21142024^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.