600-18-0Relevant articles and documents
Zn(II)-, Al(III)-, and Cu(II)-Catalyzed Decarboxylation of 2-Oxalopropionic Acid
Kubala, Gregory,Martell, Arthur E.
, p. 6602 - 6609 (1982)
Distributions of species formed by the coordination of 2-oxalopropionic acid by Zn(II), Al(III), and Cu(II) ions are presented, and kinetics of decarboxylation are discussed in terms of the species present in solution.Studies of initial rates of metal ion catalyzed decarboxylation of 2-oxalopropionic acid (H2L) show dependence on the degree of formation of the metal chelate (ML).Rate constants (kML) for the decarboxylation of ZnL, CuL, and AlL+ were found to be 18.2 x 10-3 s-1, 21.0 x 10-3 s-1, and 9.51 x 10-3 s-1, respectively.The equilibrium constants for ML(keto) ML(enol) were evaluated for the Zn(II) and Al(III) systems and rate constants (kKML) for the decarboxylation of the active keto forms of the Zn(II) and Al(III) chelates were found to be 31 x 10-3 s-1 and 79 x 10-3 s-1, respectively.The decarboxylation rate constant for the 2:1 Al(III) chelate, AlL2-, was determined to be 33.5 x 10-3 s-1.The keto-enol equilibrium constant -(enol)>/-(keto)> was evaluated, and the decarboxylation rate constant of AlL2-(keto) was calculated as 43 x 10-3 s-1.
Engineering methionine γ-lyase from Citrobacter freundii for anticancer activity
Raboni, Samanta,Revtovich, Svetlana,Demitri, Nicola,Giabbai, Barbara,Storici, Paola,Cocconcelli, Chiara,Faggiano, Serena,Rosini, Elena,Pollegioni, Loredano,Galati, Serena,Buschini, Annamaria,Morozova, Elena,Kulikova, Vitalia,Nikulin, Alexey,Gabellieri, Edi,Cioni, Patrizia,Demidkina, Tatyana,Mozzarelli, Andrea
, p. 1260 - 1270 (2018)
Methionine deprivation of cancer cells, which are deficient in methionine biosynthesis, has been envisioned as a therapeutic strategy to reduce cancer cell viability. Methionine γ-lyase (MGL), an enzyme that degrades methionine, has been exploited to selectively remove the amino acid from cancer cell environment. In order to increase MGL catalytic activity, we performed sequence and structure conservation analysis of MGLs from various microorganisms. Whereas most of the residues in the active site and at the dimer interface were found to be conserved, residues located in the C-terminal flexible loop, forming a wall of the active site entry channel, were found to be variable. Therefore, we carried out site-saturation mutagenesis at four independent positions of the C-terminal flexible loop, P357, V358, P360 and A366 of MGL from Citrobacter freundii, generating libraries that were screened for activity. Among the active variants, V358Y exhibits a 1.9-fold increase in the catalytic rate and a 3-fold increase in KM, resulting in a catalytic efficiency similar to wild type MGL. V358Y cytotoxic activity was assessed towards a panel of cancer and nonmalignant cell lines and found to exhibit IC50 lower than the wild type. The comparison of the 3D-structure of V358Y MGL with other MGL available structures indicates that the C-terminal loop is either in an open or closed conformation that does not depend on the amino acid at position 358. Nevertheless, mutations at this position allosterically affects catalysis.
Unusual stereoselectivity of methionine-γ-lyase from Citrobacterfreundii toward diastereomeric (S)-methionine S-oxide
Faleev, Nikolai G.,Tsvetikova, Marina A.,Ilyin, Mikhail M.,Yufryakov, Vyacheslav S.,Kolotyrkina, Natal'ya G.,Kulikova, Viktoria V.,Demidkina, Tatiana V.,Kochetkov, Konstantin A.
, p. 236 - 238 (2021/05/04)
Using a diastereomeric mixture of (S)-methionine S-oxide as an example, kinetic preference of methionine-γ-lyase toward a stereogenic center at the γ-sulfur atom of the (2S, RS) diastereomer was discovered for the first time.
Biocatalytic Cascade Reaction for the Asymmetric Synthesis of L- and D-Homoalanine
Silva, Marcus V. de M.,Costa, Ingrid C. R.,de Souza, Rodrigo O. M. A.,Bornscheuer, Uwe T.
, p. 407 - 411 (2018/11/01)
Unnatural amino acids attract growing attention for pharmaceutical applications as they are useful building blocks for the synthesis of a number of chiral drugs. Here, we describe a two-step enzymatic method for the asymmetric synthesis of homoalanine from L-methionine, a cheap and readily available natural amino acid. First, the enzyme L-methionine γ-lyase (METase), from Fusobacterium nucleatum, catalyzed the γ-elimination of L-methionine to 2-oxobutyrate. Second, an amino acid aminotransferase catalyzed the asymmetric conversion of 2-oxobutyrate to either L- or D-homoalanine. The L-branched chain amino acid aminotransferase from Escherichia coli (eBCAT), using L-glutamate as amino donor, produced L-homoalanine (32.5 % conv., 28 % y, 99 % ee) and the D-amino acid aminotransferase from Bacillus sp. (DATA) used D-alanine as amino donor to produce D-homoalanine (87.5 % conv., 69 % y, 90 % ee). Thus, this concept allows for the first time the synthesis of both enantiomers of this important unnatural amino acid.
