The three-dimensional structure of the external aldimine of Citrobacter freundii methionine γ-lyase with competitive inhibitor glycine has been determined at 2.45 Å resolution. It revealed subtle conformational changes providing effective binding of the inhibitor and facilitating labilization of Cα-protons of the external aldimine. The structure shows that 1, 3-prototropic shift of Cα-proton to C4'-atom of the cofactor may proceed with participation of active site Lys210 residue whose location is favorable for performing this transformation by a concerted mechanism. The observed stereoselectivity of isotopic exchange of enantiotopic Cα-protons of glycine may be explained on the basis of external aldimine structure. The exchange of Cα-pro-(R)-proton of the external aldimine might proceed in the course of the concerted transfer of the proton from Cα-atom of glycine to C4'-atom of the cofactor. The exchange of Cα-pro-(S)-proton may be performed with participation of Tyr113 residue which should be present in its basic form. The isotopic exchange of β-protons, which is observed for amino acids bearing longer side groups, may be effected by two catalytic groups: Lys210 in its basic form, and Tyr113 acting as a general acid.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1016/j.biochi.2014.01.007 | DOI Listing |
Protein Sci
January 2025
Department of Chemistry and Biochemistry, Loyola University Chicago, Chicago, Illinois, USA.
Antimicrobial resistance is a significant cause of mortality globally due to infections, a trend that is expected to continue to rise. As existing treatments fail and new drug discovery slows, the urgency to develop novel antimicrobial therapeutics grows stronger. One promising strategy involves targeting bacterial systems exclusive to pathogens, such as the transcription regulator protein GabR.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
October 2024
Department of Chemistry and Biochemistry, The Ohio State University, Columbus, OH, 43210, USA.
Non-thermal plasma discharge produced in the wake of charged microdroplets is found to facilitate catalyst-free radical mediated hydrazine cross-coupling reactions without the use of external light source, heat, precious metal complex, or trapping agents. A plasma-microdroplet fusion platform is utilized for introduction of hydrazine reagent that undergoes homolytic cleavage forming radical intermediate species. The non-thermal plasma discharge that causes the cleavage originates from a chemically etched silica capillary.
View Article and Find Full Text PDFChem Sci
August 2024
Neutron Scattering Division, Oak Ridge National Laboratory Oak Ridge TN 37831 USA
Serine hydroxymethyltransferase (SHMT) is a key enzyme in the one-carbon metabolic pathway, utilizing the vitamin B derivative pyridoxal 5'-phosphate (PLP) and vitamin B derivative tetrahydrofolate (THF) coenzymes to produce essential biomolecules. Many types of cancer utilize SHMT in metabolic reprogramming, exposing the enzyme as a compelling target for antimetabolite chemotherapies. In pursuit of elucidating the catalytic mechanism of SHMT to aid in the design of SHMT-specific inhibitors, we have used room-temperature neutron crystallography to directly determine the protonation states in a model enzyme SHMT (SHMT), which exhibits a conserved active site compared to human mitochondrial SHMT2 (hSHMT2).
View Article and Find Full Text PDFACS Catal
August 2024
Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia 30602, United States.
Tryptophan indole lyase (TIL; [E.C. 4.
View Article and Find Full Text PDFInt J Biol Macromol
March 2024
School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Benxi 117004, China. Electronic address:
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!