The Chemistry of Protein Catalysis

Understanding the Functional Roles of Amino Acid Residues in Enzyme Catalysis

“…Further, the side chains of the aliphatic amino acid (leucine, alanine, glycine, isoleucine and valine) are almost never identified as catalytic in MACiE, due more to their fundamentally catalytically inert nature than their absence from the active sites (all residue types are found to be involved in catalysis, acting through their main chain portions in MACiE enzymes). 19 Although there are rare occasions when these residues may form part of the path of an electron transfer (e.g. alanine in the nitrogenase represented by M0212 25-28 ), they are not considered further here.…”

“…From Table 2, it is clear that these functions are not completely orthogonal and indeed some are complementary to one another, often occurring in tandem. For example, proton acceptor and donor functions are by far the most common reactant function 19 and are equally common, which is to be expected. When a residue donates a proton in one step, if it is to return to a state where it can catalyse the next reaction it must re-acquire a proton from another residue, water or substrate.…”

“…This can include electrostatic stabilisation of an intermediate, transition state or other amino acid residue and may include the stabilisation of a radical species. Destabilisation is a much rarer event (there are only two cases of this function in MACiE) 19 , possibly due to human annotation rather than absence of the function, thus it is included in this functional class. Steric roles -residues that affect the outcome of the reaction through steric considerations, either hindrance through bulky side chain interactions, or more subtle directors that function in the correct steric alignment of the reacting species.…”

Identification of a Glycine Motif Required for Packing in EmrE, a Multidrug Transporter from Escherichia coli

“…In enzymatic reactions, glycine has practically nil catalytic propensity (42). In membrane proteins involved in vectorial metabolism glycine residues have been shown to play several roles, both structural and functional, some of them already described in the Introduction.…”

Riboswitch effectors as protein enzyme cofactors

“…There are several thousand chemical reactions catalyzed by enzymes, many of them requiring the participation of small molecule cofactors (Holliday et al 2007). These cofactors promote reactions that include carbon-carbon bond making and breaking, oxidation/reduction, and radical chemistry.…”