Cysteine ligand hydrogen bonding

The sulfur atom is a favorable zinc ligand because of its size and polarizability. The thiol side chain of cysteine (p/Cg —8.5) is negatively charged as it complexes a metal ion in a protein in addition to metal coordination, the cysteine thiol may simultaneously accept hydrogen bonds from other protein residues (Adman et al, 1975 Ippolito et al, 1990). Hydrogen bond networks with cysteine metal ligands are discussed further in Section I11,B. 

Fig. 11. Diagrammatic view of contacts between ethacrynic acid and deoxyhemoglobin A. The ligand is covalently bound to cysteine-93 of the p chain. and indicate fractional charges due to the electronic dipolar nature of the o-dichlorobenzene moiety. Broken lines indicate hydrogen bonds and dotted lines van der Waals contacts. Oxygen-aromatic interactions involving aspartate-94 and cysteine-93 are shown schematically. Reproduced with permission from Perutz et al. (1986).

The proposed electron transfer pathway from the proximal to the distal FeS cluster is shown in Figure 10. It involves a series of hydrogen bonds over the 16 distance between these two 4Fe clusters. The thin dotted lines indicate the most likely pathway whereas, the thick lines include two ithrough-space jumpsi, which are considered to incur a penalty in terms of electron transfer rate. The pathway is predominantly through the FeoS clusters, the cysteine ligands, and two histidines. The final site at which electrons are transferred to the electron donor or acceptor appears to be histidine 185, the ligand to the distal cluster. 

Figure 7 Cysteine ligand environment in A. den. azurin showing the two N-H-S hydrogen bonds. Distances are for the oxidized protein, with those for the reduced form in parentheses. Also shown are the hydrogen bonds made by the conserved Asn 47, which help constrain the copper site...

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