Surface enzyme cavity

Another family of superimposed surfaces is used in the study of active sites of enzymes. By superimposing approximate molecular surfaces of several molecules showing similar activity with respect to the given enzyme, a part of their envelope surface, called their union surface, can be taken as an object that approximately fills out the cavity of the enzyme [167,311,338]. The shape of the union surface (in fact, the shape of its complement) is expected to provide more information on the shape of the enzyme cavity than a surface of a single active molecule. 

Consider a given molecular contour surface G(a). If the size s of the cubes is chosen small enough, then any finite polycube P can fit within G(a). As in the two-dimensional case, we do not consider orientation constraints and we assume that the contour surface G(a) and polycube P may be translated and rotated with respect to one another the relative orientation of G(a) and the cubic grid is not fixed. In this model, the identity of a polycube is independent of its orientation. Two polycubes P and F are regarded identical if and only if they can be superimposed on one another by translation and rotation in 3D space. Note, however, that the polycube method of shape analysis and determination of resolution based similarity measures can be augmented with orientation constraints, suitable for the study of molecular recognition and shape problems in external fields or within enzyme cavities [240,243]. 

More specifically we analyze the similarities and differences between bio- and chemo-catalytic systems in the sections on oxidation and reduction catalysis. We highlight the important mechanistic concepts and energetic requirements that were described in the previous chapters such as pre-transition-state orientation and solvation (the dielectric constant of an enzyme is as low as that of a zeolite) and the match of the shape and size of the transition state with the enzyme cavity. In this context, it will be important to compare enzyme action concepts such as lock and key and induced Ht with some of the related ideas discussed in Chapter 2. We refer back to concepts in transition-metal surface catalysis in order to establish ideas on possible mechanisms. 

Upon the adsorption of the glucose molecule into the enzyme cavity, the cavity closes as observed in Fig. 7. lb. The cavity continues to change as the reaction proceeds, which helps to drive the reaction over the potential energy surface to the product state. Desorption of the product molecules requires reopening of the cavity in order to release them. This process can be aided by the coadsorption of an additional reactant molecule at a second peptide binding site (allosteric effect). This reduces the interaction between product molecules and cavity, assists desorption and decreases the tendency of the enzyme to become deactivated by product poisoning. 

Molecular volumes are usually computed by a nonquantum mechanical method, which integrates the area inside a van der Waals or Connolly surface of some sort. Alternatively, molecular volume can be determined by choosing an isosurface of the electron density and determining the volume inside of that surface. Thus, one could find the isosurface that contains a certain percentage of the electron density. These properties are important due to their relationship to certain applications, such as determining whether a molecule will fit in the active site of an enzyme, predicting liquid densities, and determining the cavity size for solvation calculations. 

Figure 12.8 A. 2-PS reaction. B. Surface representations of the CHS (left) and 2-PS (right) active site cavities are shown. The catalytic cysteines (red), the three positions that convert CHS into 2-PS (green), and the substitution that does not affect product formation (blue) are highlighted. C. TLC analysis of CHS, 2-PS, and CHS mutant enzymes. The radiogram shows the radiolabeled products produced by incubation of each protein with [14C]malonyl-CoA and either p-coumaroyl-CoA (C) or acetyl-CoA (A). Numbering of mutants corresponds to CHS with 2-PS numbering in parenthesis. Positions of reaction products and their identities are indicated.

Fats and other lipids are poorly soluble in water. The larger the accessible surface is—i. e., the better the fat is emulsified—the easier it is for enzymes to hydrolyze it (see p. 270). Due to the special properties of milk, milk fats already reach the gastrointestinal tract in emulsified form. Digestion of them therefore already starts in the oral cavity and stomach, where lipases in the saliva and gastric juice are available. Lipids that are less accessible—e.g., from roast pork—are emulsified in the small intestine by bile salts and bile phospholipids. Only then are they capable of being attacked by pancreatic lipase [4] (see p. 270). 

Any electrochemical device using a low molecular weight redox couple to shuttle electrons from the redox center of an enzyme to the surface of an indicator electrode, thereby increasing the effectiveness of amperometry in the detection of a substrate for the particular enzyme. The internal cavities of six-, seven-, and eight-membered cyclodextrins are trapezoids of revolution with larger open mouths dimensions (/. c., respective diameters of... 

The activity of 2,3-oxidosqualene cyclases is associated with microsomes, indicating their membrane-bound nature. However, the predicted amino acid sequences of these enzymes generally lack signal sequences and obvious transmembrane domains. Addition of hydrophobic membrane-localising regions to OSCs during evolution may have removed selection pressures that maintained alternate mechanisms for membrane localisation [33]. Consistent with this, there is a non-polar plateau on the surface of the A. acidocaldarius SC enzyme which is believed to be immersed in the centre of the membrane. The squalene substrate for SC is likely to diffuse from the membrane interior into the central cavity of the enzyme via this contact region [55,56]. 

Therapeutic proteins designed for nasal delivery must cross mucosal epithelial cells of about 3 mm thickness, coated with degradative enzymes. The total surface of the nasal mucosa is about 200 cm, and the nasal cavity can accommodate about 1.5 ml... 

The S2 binding cavity is a narrow cleft that can easily accommodate a peptide backbone, but with no room for a side chain. The interaction of the P2 side chain is made with the exterior surface of the enzyme. The S2 site is exposed to solvent and presents two possible interaction sites for bound inhibitors that are related by a rotation about %1. These sites consist of residues 179-180 on one side and residues 238-240 on the other. 

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