Glycerol dehydratation by the B12-independent enzyme may not involve the migration of a hydroxyl group: a computational study.
J Phys Chem B
; 116(24): 7076-87, 2012 Jun 21.
Article
em En
| MEDLINE
| ID: mdl-22626266
ABSTRACT
A combination of continuum electrostatic and density functional calculations has been employed to study the mechanism of the B(12)-independent glycerol dehydratase, a novel glycyl-radical enzyme involved in the microbial conversion of glycerol to 3-hydroxylpropionaldehyde. The calculations indicate that the dehydratation of glycerol by the B(12)-independent enzyme does not need to involve a mechanistically complicated migration of the middle hydroxyl group to one of the two terminal positions of a molecule, as previously suggested. Instead, the reaction can proceed in three elementary steps. First, a radical transfer from the catalytically active Cys433 to the ligand generates a substrate-related intermediate. Second, a hydroxyl group splits off at the middle position of the ligand and is protonated by the neighboring His164 to form a water molecule. The other active site residue Glu435 accepts a proton from one of the terminal hydroxyl groups of the ligand and a CâO double bond is created. Third, the reaction is completed by a radical back transfer from the product-related intermediate to Cys433. On the basis of our calculations, the catalytic functions of the active site residues have been suggested. Cys433 is a radical relay site; His164 and Glu435 make up a proton accepting/donating system; Asn156, His281, and Asp447 form a network of hydrogen bonds responsible for the electrostatic stabilization of the transition state. A synergistic participation of these residues in the reaction seems to be crucial for the catalysis.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vitamina B 12
/
Modelos Moleculares
/
Hidroliases
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Alemanha