3AO0

Crystal structure of ethanolamine ammonia-lyase from Escherichia coli complexed with CN-CBL and (S)-2-amino-1-propanol

Summary for 3AO0

• Entry DOI: 10.2210/pdb3ao0/pdb
• Related: 3ABO 3ABQ 3ABR 3ABS 3ANY
• Descriptor: Ethanolamine ammonia-lyase heavy chain, Ethanolamine ammonia-lyase light chain, (2S)-2-aminopropan-1-ol, ... (6 entities in total)
• Functional Keywords: (beta/alpha)8 fold, cobalt, lyase, cobalamin, tim barrel
• Biological source: Escherichia coli; More
• Total number of polymer chains: 4
• Total formula weight: 159267.60

Authors

Shibata, N. (deposition date: 2010-09-16, release date: 2011-08-03, Last modification date: 2023-11-15)

Primary citation

Shibata, N.,Higuchi, Y.,Toraya, T.
How coenzyme B12-dependent ethanolamine ammonia-lyase deals with both enantiomers of 2-amino-1-propanol as substrates: structure-based rationalization.
Biochemistry, 50:591-598, 2011

PubMed Abstract: 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 Valα326 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 Pheα329 and Leuα402 residues.

PubMed: 21142024
DOI: 10.1021/bi101696h

Experimental method

X-RAY DIFFRACTION (2.25 Å)