Proteins side-chain reactions

Scheme 10.31 Reaction cycle of KG-dependent (KG = a-keto-glutarate) enzymes. Metal ligands from protein side chains and water are omitted for clarity. One of the oxygens of O2 is incorporated into succinate. The other oxygen is either incorporated into the product or reduced to water depending on the nature of the reaction.

Bakhshi, A. K., and J. Ladik. 1986. Ab Initio Study of the Effect of Side-Chain Reactions on the Electronic Structure of Proteins. Chem. Phys. Letters 129, 269-274. 

Harry B. Gray and Walther Ellis,13 writing in Chapter 6 of reference 13, describe three types of oxidation-reduction centers found in biological systems. The first of these, protein side chains, may undergo oxidation-reduction reactions such as the transformation of two cysteine residues to form the cystine dimer as shown in equation 1.28 ... 

In addition, we can meet examples of covalent bonding that are responsible for binding a substrate, where a functional group in the substrate reacts chemically with a protein side-chain functional group. Two important reactions are ... 

Although effects of hydration are important in almost all biochemical equilibria, they are difficult to assess quantitatively. It is hard to know how many molecules of water are freed or immobilized in a given reaction. Charged groups in proteins are often hydrated. However, if they are buried in the interior of the protein, they may be solvated by polarizable protein side chain groups such as -OH or by backbone or side chain amide groups.57 58... 

Photosynthetic phosphorylation of protein side chains 79 substrate level 775, 800 Phosphorylation, photosynthetic. See Photosynthetic phosphorylation Phosphorylation reactions 303 Phosphorylation state ratio definition of 303 O-Phosphoserine 610s Phosphoserine 545 Phosphothreonine 545 Phosphotransferase system bacterial 419,420 Phosphotransferases 637... 

It is the purpose of this review to discuss some of the better known biological enamines. Due to the preoccupation of the author with thiamin chemistry and enzymology, many of the properties of enamines will be exemplified by a variety of results obtained on this particular system. Enamines are, however, present in a number of other biochemical processes as well, where their remarkably rich chemistry is required. In most of these reactions the enamines are only present as intermediates, that are the result of covalent catalysis, in which the substrate of the enzymatic reaction forms a covalent bond with either a protein side chain or a required coenzyme. 

Perhaps a more challenging question is how we can discover new PTM reactions. In principle, there are analytic tools that can be used to research this topic. One such tool is top-down FT-MS, which determines the molecular weight of the whole protein with high accuracy. By comparing the obtained tandem MS (MS/MS) result with the expected MS/MS result, post-translational modifications can be identified (150). Crystallography can also discover new PTM, if a protein expressed in the proper host can be crystallized. Some rare modifications or protein side chains were discovered this way (151). However, the success of using these methods would require that... 

Chorismate mutase provides an example of an enzyme where QM/MM calculations have identified an important catalytic principle at work [8], This enzyme catalyses the Claisen rearrangement of chorismate to prephenate. The reaction within the enzyme is not believed to involve chemical catalysis, and this pericylic reaction also occurs readily in solution. Lyne et al. [8] investigated the reaction in chorismate mutase in QM/MM calculations, at the AMI QM level (AMI was found to perform acceptably well for this reaction in comparisons with ab initio results for the reaction in the gas phase [8]). Different sizes of QM system were tested in the QM/MM studies (e.g. including the substrate and no, or up to three, protein side chains), and similar results found in all cases. The reaction was modelled by minimization along an approximate reaction coordinate, defined as the ratio of the forming C-C and breaking C-0 bonds. Values of the reaction coordinate were taken from the AMI intrinsic reaction coordinate for the gas-phase reaction. 

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