The Different Types of PCET in Biology

Nature provides striking examples of each of the types of PCET discussed in this chapter. Enzymes often rely on PCET to affect primary metabolic steps involving charge transport and catalysis. Amino acid radical generation and transport is synonymous with PCET [187], as is the activation of substrate bonds at enzyme active sites [29]. PCET is especially prevalent for metallo-cofactors that activate 

Type A PCET reactions describe amino acid radical generation steps in many enzymes, since the electron and proton transfer from the same site as a hydrogen atom [188]. Similarly, substrate activation at C-H bonds typically occurs via a Type A configuration at oxidized cofactors such as those in lipoxygenase [47, 48] galactose oxidase [189-191] and ribonucleotide reductase (Y oxidation at the di-iron cofactor, vide infra) [192]. Here, the HATs are more akin to the transition metal mediated reactions of Section 17.3.1 since the final site of the electron and proton are on site differentiated at Ae (redox cofactor) and Ap (a ligand). 

The studies on these Hangman porphyrins and other macrocyclic Hangman platforms [205] clearly demonstrate that exceptional catalysis may be achieved when redox and PT properties of a cofactor are controlled independently. A key requirement is that the PT distance is kept short, which may be accomplished by orthogonalizing ET and PT coordinates. The benefits of incorporating PT functionality into redox catalysis can only be realized when a suitable geometry is established. Moreover, the Hangman platforms show that a multifunctional activity of a single metalloporphyrin-based scaffold is achieved by the addition of proton control to a redox platform. This observation is evocative of natural heme-de-pendent proteins that employ a conserved protoporphyrin IX cofactor to affect a myriad of chemical reactivities. 

Other oxidases also derive function from bidirectional PCET pathways at the enzyme active site. The recent crystal structures of PSII [206, 207] support suggestions that as the oxygen evolving complex (OEC) steps through its various S-states [208, 209], substrate derived protons are shuttled to the lumen via a proton exit channel, the headwater of which appears to be the Dgi residue hydrogen-bonded to Mn-bound water [210]. The protons are liberated with the proton-coupled oxidation of the Mn-OH2 site. As shown by the structure reproduced in Fig. 17.23, Dgj is diametrically opposite to Y, which has long been known [148, 151, 152] to be the electron relay between the PS II reaction center and OEC. Notwithstanding, 

Bidirectional PCET is also featured on the reduction side of the photosynthetic apparatus. In the bacterial photosynthetic reaction center, two sequential photo-induced ET reactions from the P680 excited state to a quinone molecule (Qg) are coupled to the uptake of two protons to form the hydroquinone [213-215]. This diffuses into the inter-membrane quinone pool and is re-oxidized at the Qq binding site of the cytochrome bcj and coupled to translocation of the protons across the membrane, thereby driving ATP production. These PCET reactions are best described by a Type D mechanism because the PCET of Qg appears to involve specifically engineered PT coordinates among amino acid residues [215]. In this case PT ultimately takes place to and from the bulk solvent. Coupling remains tight in 

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