Cysteine biochemical structure

Neither structure provides a direct view on the catalytic mechanism of these enzymes. However, prior biochemical and structural studies on bacterial MTases in complex with DNA revealed a mechanism involving base-flipping followed by a nudeophilic attack of a conserved cysteine on carbon C6 of the cytosine to be... 

The structure and mechanism of catalysis of FTase were well defined in the late 1990s from several X-ray crystallography and elegant biochemical studies [24,26-30]. The enzyme is a heterodimer of a and P subunits [31,32]. The P subunit contains binding sites for both the farnesyl pyrophosphate and the CAAX protein substrates. A catalytic zinc (Zn " ) identified in the active site of the P subunit participates in the binding and activation of the CAAX protein substrates [28]. The Zn " is coordinated to the enzyme in a distorted tetrahedral geometry and surrounded by hydrophobic pockets [24,27]. Upon binding of the CAAX peptide, the thiol of the cysteine displaces water and is activated for a nucleophilic attack via thiolate on the C-1 carbon atom of farnesyl pyrophosphate [30]. 

Fig. 1. Structure of CoA, composed of three parts a nucleotide pan derived from 3 -adenosine-5 -pbosphate, forming a phosphodiester bond with a 4-phospho derivative of pantothenic acid, and a third pan derived horn the amino acid, cysteine. The side chain SH group of the latter is ftee in this compound and is readily acylated, and thus able to act as a carrier for acyl groups in biochemical reactions in which it transfers that group between two substrates...

Kidric, M., Fabian, H., Brzin, J., Popovic, T., and Pain, R.H. 2002. Folding, stability, and secondary structure of a new dimeric cysteine proteinase inhibitor. Biochem. Biophys. Res. Commun. 297 962-967. 

Jose-Estanyol, M., Gomis-Ruth, F. X., and Puigdomenech, P. (2004). The eight-cysteine motif, a versatile structure in plant proteins. Plant Physiol. Biochem. 42,355-365. 

Deterding, L. J., Srinivas, P., Mahmood, N. A., Burka, L. T., and Tomer, K. B. (1989). Fast atom bombardment and tandem mass spectrometry for structure determination of cysteine, N- acety I cyste i n e, and glutathione adducts of xenobiotics. Anal. Biochem. 183 94-107. 

Cytochrome-c Oxidase. Readers are referred to a comprehensive review [84] on this enzyme. Considerable advances are from two recent protein x-ray structures [85,86], now detailing the general picture previously provided by biochemical and spectroscopic studies. A cysteine-bridged dinuclear CuA center... 

HRV Arnstein, D Morris. The structure of a peptide, containing alpha-aminoadipic acid, cysteine and valine, present in the mycelium of Penicillium chrysogenum. Biochem J 76 357-361, 1960. 

The structure that emerges from the physical and biochemical studies is one that contains a 5-6 coordinate Ni atom in a mixed ligand environment, featuring at least two cysteinate ligands and one site that is available for binding exogenous ligands. 

Salvesen, G., Parkes, C., Abrahamson, M., Grubb, A., and Barrett, A. J., Human low-Mr Kinino-gen contains three copies of a cystatin sequence that are divergent in structure and in inhibitory activity for cysteine proteinases. Biochem. J. 234(2), 129 131 (1986). 

The structure of the bacterial ArsC from Escherichia coli plasmid R773 has been solved at 1.65 A resolution, and revealed that arsenate reductase (ArsC) has only one cysteine residue (Cys-12) in the active site, surrounded by an arginine triad composed of Arg-60, Arg-94, and Arg-107 (Mukhopadhyay et al, 2002). However, the arsenate reductase from Staphylococcus aureus has three cysteine residues (Cys-10, Cys-82, and Cys-89). The biochemical and mutational studies established that the arsenate binds to the triad of arginine (Arg-60, Arg-94, and Arg-107) residues and forms a covalent bond with the cysteine (Cys-12) residue near the N-terminus at the active site of arsenate reductase and/or participates in catalysis (Rosen, 2002a Silver and Phung, 2005 Shi etal, 2003 Martin et al, 2001). 

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