Big Chemical Encyclopedia

Chemical substances, components, reactions, process design ...

Articles Figures Tables About

Active site protein

The main lesson from the analysis given above is that the activation free energy of the reaction is strongly correlated with the stabilization of the ionic resonance structure by the protein-active site. The generality of this concept will be considered in the following chapters. [Pg.149]

FIGURE 6.6. The type of model compounds that were used to estimate the electrostatic stabilization in lysozyme (the only hydrogen atom shown, is the one bonded to the oxygen). Such molecules do not show a large rate acceleration due to electrostatic stabilization of the positively charged carbonium transition state. However, the reaction occurs in solution and not in a protein-active site, and the dielectric effect is expected to be very different in the two cases. [Pg.159]

After the somewhat tedious parametrization procedure presented above you are basically an expert in the basic chemistry of the reaction and the questions about the enzyme effect are formally straightforward. Now we only want to know how the enzyme changes the energetics of the solution EVB surface. Within the PDLD approximation we only need to evaluate the change in electrostatic energy associated with moving the different resonance structures from water to the protein-active site. [Pg.167]

The actual calculations that compare the energetics of the EVB configurations in the protein-active site and solutions are summarized in Fig. 6.10. [Pg.168]

To realize the reason for this result from a simple intuitive point of view it is important to recognize that the ionized form of Aspc is more stable in the protein-active site than in water, due to its stabilization by three hydrogen bonds (Fig. 7.7). This point is clear from the fact that the observed pKa of the acid is around 3 in chymotrypsin, while it is around 4 in solution. As the stability of the negative charge on Aspc increases, the propensity for a proton transfer from Hisc to Aspc decreases. [Pg.184]

Solution 8.5. First, use the LD model to calculate the Ag of w [the results should be -25, -220, and -190 kcal/mol for Ag , Ag2 and Ag, respectively]. Now you should repeat the calculations, modeling the protein-active site that includes the Zn2+ ion as well as the other protein residues by the PDLD model. [Pg.200]

Enzyme active sites, 136,148, 225. See also Protein active sites in carbonic anhydrase, 197-199 in chymotrypsin, 173 in lysozyme, 153, 157 nonpolar (hypothetical site), 211-214 SNase, 189-190,190 steric forces in, 155-158, 209-211, 225 in subtilisin, 173 viewed as super solvents, 227 Enzyme cofactors calcium ... [Pg.231]

PRO SELECT One of the first reported tools for the virtual screening of libraries for fit into a protein active site Protherics Molecular Design Ltd. http //www.protherics. com [30]... [Pg.359]

The current example illustrates PVDOS formulation as an effective basis for comparison of experimental and theoretical NIS data for ferrous nitrosyl tetraphe-nylporph3Tin Fe(TPP)(NO), which was done [101] along with other ferrous nitrosyl porphyrins. Such compounds are designed to model heme protein active sites. In particular, the elucidation of the vibrational dynamics of the Fe atom provides a unique opportunity to specifically probe the contribution of Fe to the reaction dynamics. The geometrical structure of Fe(TPP)(NO) is shown in Fig. 5.16. [Pg.193]

Fig. 8 Schematic representation of the binding of a small molecule (left) or a fragment (right) to a hypothetical protein active site... Fig. 8 Schematic representation of the binding of a small molecule (left) or a fragment (right) to a hypothetical protein active site...
De novo design approaches computationally generate virtual molecules based on protein active sites or simply just de noco-designed molecules [39]. [Pg.414]

It is not a trivial matter to get a converged value for these simulations, since in both we are forcing the substrate to vanish from the system a substantial mutation. But if one has copious computer time available and is careful, one has the potential for calculating such a value provided the substrate is not too large and there are not appreciable large-scale changes in the protein active site upon binding. [Pg.17]

Classical electrostatic modeling based on the Coulomb equation demonstrated that the model system chosen could account for as much as 85% of the effect of the protein electric field on the reactants. Several preliminary computations were, moreover, required to establish the correct H-bond pattern of the catalytic water molecule (WAT in Fig. 2.6). Actually, in the crystal structure of Cdc42-GAP complex [60] the resolution of 2.10 A did not enable determination of the positions of the hydrogen atoms. Thus, in principle, the catalytic water molecule could establish several different H-bond patterns with the amino acids of the protein-active site. Both classical and quantum mechanical calculations showed that WAT, in its minimum-energy conformation,... [Pg.59]

Fe 2S], a [4Fe-4S] and a [3Fe-4S] center. The enzyme catalyzes the reversible redox conversion of succinate to fumarate. Voltammetry of the enzyme on PGE electrodes in the presence of fumarate shows a catalytic wave for the reduction of fumarate to succinate (much more current than could be accounted for by the stoichiometric reduction of the protein active sites). Typical catalytic waves have a sigmoidal shape at a rotating disk electrode, but in the case of succinate dehydrogenase the catalytic wave shows a definite peak. This window of optimal potential for electrocatalysis seems to be a consequence of having multiple redox sites within the enzyme. Similar results were obtained with DMSO reductase, which contains a Mo-bis(pterin) active site and four [4Fe 4S] centers. [Pg.392]

The use of models that mimic a protein active site is normally prompted by the desire to eliminate any influence of the polypeptide backbone surrounding the active site in real biological molecules, which may obscure its physico-chemical properties. The first attempts to synthesize metal complexes similar to the active site of haemoproteins, through the use of simple metalloporphyrin derivatives, failed. The failure was due to the fact that these complexes react irreversibly with dioxygen as a consequence of side autooxidative reactions of the type ... [Pg.452]

The type 1-3 terminology to distinguish different Cu protein active sites remains extremely useful. Sub-groupings are appearing however in all three categories particularly in the case of the binuclear (EPR inactive) type 3 centers. Thus, in the recently determined X-ray crystal structure of ascorbate oxidase the type 3 and type 2 centers are present as a single trimer unit [. A discrete binuclear type 3 center is, however, retained in hemocyanin [6]. [Pg.175]

The coupling of the GPC spin column/ESI-MS screening results with NMR (2D HSQC) is a powerful method for confirming that the non-covalent binders identified by the MS experiments truly bind at the predicted active site by observing NMR chemical shift perturbations in the vicinity of the protein active site [1, 15]. In contrast, the absence of chemical shift perturbations or a random distribution of chemical shift changes on the protein surface would imply a lack of an interaction of the compound with the protein or potentially the existence of non-specific binding. The development of the GPC spin column/MS/NMR assay... [Pg.105]

Obtaining MS EC50S and Kf S for Ligands Non-covalently Bound to Protein Active Sites... [Pg.112]

However, none of the above-mentioned databases are directly usable to generate a collection of druggable protein active sites customized to accommodate small molecular-weight drug-like ligands. Generally, no... [Pg.110]

CPASS (comparison of protein active site structures) (91) http //www.bionmr-c 1. unl.edu/CPASS OV/... [Pg.156]

Comparison of protein active site structures for functional annotation of proteins and drug design. Proteins 65 124-135... [Pg.164]

The synthesis, structures, and properties of analogs of iron-sulfur protein active sites has been recently reviewed by Venkateswara Rao and Holm [5]. In the order of increasing iron content, these sites are of Fe(SR)4, Fe2S2(SR)4, Fe3S4(SR)4, or Fe3S4(SR)3, and Fe4S4(SR)4 stoichiometry (cf. Fig. 2) and are now briefly treated. [Pg.595]

Chemoselectivity and regioselectivity are enzymatic properties of significant synthetic interest [1]. Their common feature is the fact that the enzymatic preference toward one of the several functional groups present on a substrate molecule is dictated by its accessibility to the protein active site (steric effect) and not necessarily by its chemical reactivity. [Pg.145]


See other pages where Active site protein is mentioned: [Pg.144]    [Pg.159]    [Pg.182]    [Pg.184]    [Pg.233]    [Pg.285]    [Pg.34]    [Pg.23]    [Pg.107]    [Pg.769]    [Pg.394]    [Pg.398]    [Pg.41]    [Pg.42]    [Pg.80]    [Pg.86]    [Pg.441]    [Pg.123]    [Pg.223]    [Pg.27]    [Pg.104]    [Pg.195]    [Pg.200]    [Pg.212]    [Pg.245]    [Pg.80]   
See also in sourсe #XX -- [ Pg.70 , Pg.77 ]




SEARCH



Active site of proteins

Active site protonations, blue copper proteins

Active-Site and Protein Models

Activity-based protein profiling (ABPP site-directed

Cobalt An Excellent Spectroscopic Probe for Protein Active Sites

Comparison of Protein Active-Site Structures

Copper proteins active site nature

Copper proteins active sites

Heme proteins iron active site

Protein disulfide oxidoreductase from active sites

Protein disulfide-isomerase active site

Protein tyrosine phosphatases Active site

Ribosome-inactivating proteins active site

Sulfate binding protein active site

© 2024 chempedia.info