The Role of O-acetylserine Sulfhydrylase in Cysteine Biosynthesis in Salmonella tryphimurium:
             A structural and functional Analysis
            
            
             Introduction
             Pyridoxial 5'-phosphate (PLP) acts as a cofactor in many enzymes involved in diverse aspects of amino acid metabolism such as transamination, β/γ-elimination, β/γ-replacement and racemization. In all PLP-dependant enzymes the carbonyl group of the PLP coenzyme binds to an ε-amino group of a lysine residue in the active site, forming an internal aldimine. O-Acetylserine sulfahydrylase (OASS), isolated from Salmonella typhimurium, belongs to the β -family of PLP-dependant enzymes and catalyzes the last step in the cysteine biosynthesis pathway via β-replacement, converting O-acetylserine (OAS) to cysteine, upon exchanging acetate in the OAS side chain for sulfide (Fig. 1). The structural and functional framework underlying the reaction mechanism for OASS has been characterized extensively by kinetic studies, site-directed mutagenesis, UV-visible fluorescence and phosphorescence spectroscopy and x-ray structural determination. Three conformationally distinct "open", "closed", and "inhibited" states were elucidated.
            
             Overall Topology and Protein Folding
             The structures of all proteins can be described in a hierarchical manner relating four levels of organization. The primary level is the amino acid sequence. The secondary level is constructed by motifs in backbone conformations, stabilized by hydrogen bonding, such as helices and β-sheets. Tertiary structure describes the complete folded three-dimensional shape of a single chain, and quaternary structure is the association of folded chains to make oligomeric proteins. The nature of the final folded protein, including quaternary structure, is the net result of both enthalpic (ΔH) and entropic (ΔS) optimization to achieve the lowest or most negativ...