Cysteine synthase complex

Fig. 6 Biochemical conversion of serine to cysteine by the enzymes of the cysteine synthase complex (Adapted from [57])...

Francois, J.A. et al. (2006) Structural basis for interaction of O-acetylserine sulfhydrylase and serine acetyltransferase in ibc Arabidopsis cysteine synthase complex. Plant Cell 18,3647 3655... 

Step 2, another priming reaction, involves a further exchange of thioester linkages by another nucleophilic acyl substitution and results in covalent bonding of the acetyl group to a cysteine residue in the synthase complex that will catalyze the upcoming condensation step. 

This enzyme, catalyzing Eq. (1), has been demonstrated in a number of plants (Smith and Thompson, 1%9 Ngo and Shargool, 1974 Ascano and Nicholas, 1977). The 54-fold purified enzyme from kidney bean seedlings (Smith and Thompson, 1971) had values of 6 x lO IW for serine and 2 x Qr M for acetyl-CoA. The enzyme does not catalyze the acetylation of homoserine or threonine. Activities with other acyl-CoA derivatives were not tested. During purification, this enzyme was separated fix>m cysteine synthase, in contrast to the serine acetyltransferase from SalmoneUa typhimurium which has been isolated predominantly complexed with cysteine synthase (Kredich et al., 1969). 

The characteristics of cyanobacterial products is richness of peptides, especially modified peptides. Most modified peptides from marine cyanobacteria contains thiazole and thiazoline rings derived from cysteine. These peptides are generally produced by poleketide synthase and nomibosomal peptide synthase complexes (PKS/NRPS), which are exciting topics in antibiotics research. A number of researchers are exploring these genes from cyanobacteria as well. 

Wirtz, M. and Hell, R. (2006) Functional analysis of the cysteine synthase protein complex from plants Stmctural, biochemical and regulatory properties. J. Plant Physiol 163, 273-286... 

Figure 21-2. Fatty acid synthase multienzyme complex. The complex is a dimer of two identical polypeptide monomers, 1 and 2, each consisting of seven enzyme activities and the acyl carrier protein (ACP). (Cys— SH, cysteine thiol.) The— SH of the 4 -phosphopantetheine of one monomer is in close proximity to the— SH of the cysteine residue of the ketoacyl synthase of the other monomer, suggesting a "head-to-tail" arrangement of the two monomers. Though each monomer contains all the partial activities of the reaction sequence, the actual functional unit consists of one-half of one monomer interacting with the complementary half of the other. Thus, two acyl chains are produced simultaneously. The sequence of the enzymes in each monomer is based on Wakil.

Figure 8-2. Pathway for synthesis of palmitate by the fatty acid synthase (FAS) complex. Schematic representation of a single cycle adding two carbons to the growing acyl chain. Formation of the initial acetyl thioester with a cysteine residue of the enzyme preceded the first step shown. Acyl carrier protein (ACP) is a component of the FAS complex that carries the malonate covalently attached to a sulfhydryl group on its phosphopantatheine coenzyme (-SH in the scheme).

Couture, M., Adak, S., Stuehr, D.J., Rousseau, D. L. (2001) Regulation of the properties of the heme-NO complexes in nitric-oxide synthase by hydrogen bonding to the proximal cysteine, 7. Biol. Chem. 276, 38280-38288. 

Fig. 9. Redox-active amino acid residues related to tyrosine, (a) Tyrosine, the redox center in ribonucleotide reductase, prostaglandin H synthase, and the photosynthetic oxygen evolving complex, (b) 2,4,5-Trihydroxyphenylalanine, the redox cofactor of the quinoprotein amine oxidase, (c) Tyrosine-cysteine (Tyr-Cys), the redox cofactor of galactose oxidase.

A structural analog for the Cys4Zn motif of the ADA protein is constituted by the thiolate complex [ZnSPh(Tmph)].132 Related cadmium complexes have been also described.149 These studies are also pertinent to other enzymes that feature cysteine thiolate alkylation such as methionine synthase, methanohcoenzyme methyltransferase, farnesyl transferase. 

The polyketide synthesis chemically and biochemically resembles that of fatty acids. The reaction of fatty acid synthesis is inhibited by the fungal product ceru-lenin [9]. It inhibits all known types of fatty acid synthases, both multifunctional enzyme complex and unassociated enzyme from different sources like that of some bacteria, yeast, plants, and mammalians [10]. Cerulenin also blocks synthesis of polyketides in a wide variety of organisms, including actinomycetes, fungi, and plants [11, 12]. The inhibition of fatty acid synthesis by cerulenin is based on binding to the cysteine residue in the condensation reaction domain [13]. Synthesis of both polyketide and fatty acids is initiated by a Claisen condensation reaction between a starter carboxylic acid and a dicarboxylic acid such as malonic or methylmalonic acid. An example of this type of synthesis is shown in Fig. 1. An acetate and malonate as enzyme-linked thioesters are used as starter and extender, respectively. The starter unit is linked through a thioester linkage to the cysteine residue in the active site of the enzymatic unit, p-ketoacyl ACP synthase (KS), which catalyzes the condensation reaction. On the other hand, the extender... 

A mechanism consistent with this substantial body of evidence is shown in Fig. 57. Addition of cysteine to C-6 followed by attack of the C-5 enolate on the methylene group of CH2H4folate occurs in analogy with the mechanism suggested for the normal methylation reaction. With 5-fluoro-dUMP, however, the synthase appears to become frozen in this covalent ternary complex, resulting in loss of activity. 

Figure 8 Chalcone and HMG-CoA synthase, (a) Chalcone synthase from Alfalfa complexed with naringenin (NAR, slate) (Icgk.pdb) superimposed on the structure of the C164A mutant complexed with malonyl-CoA (slate) (Icml.pdb). Residues shown in gray are from the NAR-enzyme complex, (b) HMG-CoA synthase from S. aureus complexed with acetoacetyl-CoA (AcAc-CoA). The active site cysteine in this structure is acetylated (Ixpk.pdb ).

---