Proteins environments

J Li, MR Nelson, CY Peng, D Bashford, L Noodleman. Incorporating protein environments in density functional theory A self-consistent reaction field calculation of redox potentials of [2Ee2S] clusters in feiTedoxm and phthalate dioxygenase reductase. J Phys Chem A 102 6311-6324, 1998. 

VS Shenoy. Contribution of Protein Environment to Redox Potentials of Rubredoxm and Cytochrome c. M.S. Thesis. Pullman, WA Washington State University, 1992. 

It is generally believed that the absorption (and fluorescence excitation) peak at about 400 nm is caused by the neutral form of the chro-mophore, 5-(p-hydroxybenzylidene)imidazolin-4-one, and the one in the 450-500 nm region by the phenol anion of the chromophore that can resonate with the quinoid form, as shown below (R1 and R2 represent peptide chains). However, the emission of light takes place always from the excited anionic form, even if the excitation is done with the neutral form chromophore. This must be due to the protein environment that facilitates the ionization of the phenol group of the chromophore. This is also consistent with the fact that the pACa values of phenols in excited state are in an acidic range, between 3 and 5 (Becker, 1969), thus favoring anionic forms at neutral pH. 

The rate of protonation may vary according to the structure of the light-emitter and the environment around the light emitter. In the case of chemiluminescence reactions in solutions, the hydrophobicity, permittivity (dielectric constant) and protogenic nature of the solvent are important environmental factors. In the case of bioluminescence involving a luciferase or photoprotein, the protein environment surrounding the light-emitter will be a crucial factor. 

Lithium dodecyl sulfate causes dramatic perturbations of the protein environment of the B800-850 light-harvesting protein of Rhodopseudomonas acido-... 

After learning to estimate AG7" and AS, we might ask how AASf is affected by the steric restriction of the protein environment. As is clear from eq. (9.7), we need the differences between the entropic contributions to A G rather than the individual AS. This requires the examination of the difference between the potential surfaces of the protein and solution reaction. Here we exploit the fact that the electrostatic potential changes rather slowly and use the approximation... 

Capozzi F, Ciurli S, Luchinat C (1998) Coordination Sphere Versus Protein Environment as Determinants of Electronic and Functional Properties of Iron-Sulfur Proteins 90 127-160... 

Teigen SW, Andersen RA, Daae HL, Skaare JU. 1999. Heavy metal content in liver and kidneys of grey seals Halichoerus grypus) in various life stages correlated with metallothionein levels some metal-binding characteristics of this protein. Environ Toxicol Chem 18 2364-2369. 

Enzymes that catalyze redox reactions are usually large molecules (molecular mass typically in the range 30-300 kDa), and the effects of the protein environment distant from the active site are not always well understood. However, the structures and reactions occurring at their active sites can be characterized by a combination of spectroscopic methods. X-ray crystallography, transient and steady-state solution kinetics, and electrochemistry. Catalytic states of enzyme active sites are usually better defined than active sites on metal surfaces. 

Figure 17.5 The protein environment around the Cu centers (gold spheres) of laccase from Melanocarpus albomyces (PDB file IGWO) showing a substrate O2 molecule bound in the trinuciear Cu site [Hakulinen et al., 2002], The protein is depicted in stick representation with atoms in their conventional coloring. (Courtesy of Armand W. J. W. Tepper.) (See color insert.)...

Loew GH, Harris DL. 2000. Role of the heme active site and protein environment in structure, spectra and function of the cytochrome P450s. Chem Rev 100 407. 

In the present article, we will at first briefly overview the ONIOM methodology, with an illustration of a benchmark test of a three-layer ONIOM(QM QM MM) method, which we consider a method of future. Then we will review our recent studies of biocatalysis in which we used the ONIOM(QM MM) method to examine the effects of protein environments on the mechanisms of enzymatic reactions, with an emphasis on metalloenzymes. 

For the present reaction, the presence of surrounding protein only marginally affects the barrier (it increases by 0.7 kcal/mol). A possible reason for the small protein effects could be that in the present model, the active site is not deeply buried inside the enzyme instead it is located on the interface of two monomers. Still, addition of the protein environment had effects on the active-site geometry. The reason this does not affect the total barrier height is that when comparing transition state and reactant, the protein effect appears to be relatively constant. 

A common way to benefit from the ability to combine different molecular orbital methods in ONIOM is to combine a DFT or ab-initio description of the reactive region with a semi-empirical treatment of the immediate protein environment, including up to 1000 atoms. Due to the requirement for reliable semi-empirical parameters, as discussed in Section 2.2.1, this approach has primarily been used for non-metal or Zn-enzymes. Examples include human stromelysin-1 [83], carboxypeptidase [84], ribonucleotide reductase (substrate reaction) [85], farnesyl transferase [86] and cytosine deaminase [87], Combining two ab-initio methods of different accuracy is not common in biocatalysis applications, and one example from is an ONIOM (MP2 HF) study of catechol O-methyltransferase [88],... 

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