Alliin is a suicide substrate of Citrobacter freundii methionine γ-lyase: structural bases of inactivation of the enzyme.
The interaction of Citrobacter freundii methionine γ-lyase (MGL) and the mutant form in which Cys115 is replaced by Ala (MGL C115A) with the nonprotein amino acid (2R)-2-amino-3-[(S)-prop-2-enylsulfinyl]propanoic acid (alliin) was investigated. It was found that MGL catalyzes the β-elimination reaction of alliin to form 2-propenethiosulfinate (allicin), pyruvate and ammonia. The β-elimination reaction of alliin is followed by the inactivation and modification of SH groups of the wild-type and mutant enzymes. Three-dimensional structures of inactivated wild-type MGL (iMGL wild type) and a C115A mutant form (iMGL C115A) were determined at 1.85 and 1.45 Å resolution and allowed the identification of the SH groups that were oxidized by allicin. On this basis, the mechanism of the inactivation of MGL by alliin, a new suicide substrate of MGL, is proposed.
Engelhardt Institute of Molecular Biology, Russian Academy of Science, Vavilov Str. 32, Moscow 119991, Russian Federation.
Elena A
EA
Morozova
Engelhardt Institute of Molecular Biology, Russian Academy of Science, Vavilov Str. 32, Moscow 119991, Russian Federation.
Svetlana V
SV
Revtovich
Engelhardt Institute of Molecular Biology, Russian Academy of Science, Vavilov Str. 32, Moscow 119991, Russian Federation.
Natalya V
NV
Anufrieva
Engelhardt Institute of Molecular Biology, Russian Academy of Science, Vavilov Str. 32, Moscow 119991, Russian Federation.
Vitalia V
VV
Kulikova
Institute of Protein Research, Russian Academy of Sciences, Puschino 142290, Russian Federation.
Alexey D
AD
Nikulin
Engelhardt Institute of Molecular Biology, Russian Academy of Science, Vavilov Str. 32, Moscow 119991, Russian Federation.
Tatyana V
TV
Demidkina
D013437:Carbon-Sulfur Lyases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016971:Citrobacter freundii / Q000737:chemistry / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism; D004789:Enzyme Activation; D008958:Models, Molecular; D017354:Point Mutation; D011487:Protein Conformation
C006453:alliin; D013437:Carbon-Sulfur Lyases; C021558:L-methionine gamma-lyase; D003545:Cysteine
alliin; methionine γ-lyase