Three-dimentional structure

Uncovering of the three dimentional structure of catalytic groups at the active site of an enzyme allows to theorize the catalytic mechanism, and the theory accelerates the designing of model systems. Examples of such enzymes are zinc ion containing carboxypeptidase A 1-5) and carbonic anhydrase6-11. There are many other zinc enzymes with a variety of catalytic functions. For example, alcohol dehydrogenase is also a zinc enzyme and the subject of intensive model studies. However, the topics of this review will be confined to the model studies of the former hydrolytic metallo-enzymes. 

G. J. Davies and C. Martinez-Fleites, The O-GlcNAc modification Three-dimentional structure, enzymology and the development of selective inhibitors to probe disease, Biochem. Soc. Trans., 38 (2010) 1179-1188. 

A representative collection of various applications of Zn NMR will be described in this section. As already mentioned in a previous section, the zinc ion is responsible for protein folding and catalytic binding of H2O or CO2. For all these cases, NMR spectroscopy was a powerful tool in order to clarify the three-dimentional structure of metaUoenzymes. 

Viswanadhan, V., A. Ghose, G. Revankar, and R. Robins. 1989. Atomic Physicochemical Parameters for Three-dimentional Structure-directed QSAR.. Chem. Inf. Comput. Sci. 29, 163-172. 

Pepsin (EC 3.4.23.1) is a typical aspartic proteinase produced in the gastric mucosa of vertebrates as a zymogen form [10], This enzyme has been extensively characterized, and its three-dimensional structure has been determined at high resolution. Porcine pepsin, in particular, has been studied as model to analyze the structure-function relationship of the aspartic proteinases. Although the aspartic proteinases including mammalian and fungal enzymes are quite similar in their three-dimentional structures, there are drastic differences in the catalytic properties, especially in substrate specificities. 

Having established the three-dimentional structure of carbocations as planar, we can now study the stereochemical progression of Sk 1 reactions as compared to Sk2 reactions. As shown in Scheme 5.6, the stereochemical course of an Sk2 reaction is well defined because nucleophilic displacement of a leaving group proceeds with inversion of stereochemistry. Thus, the stereochemical outcome is defined by the stereochemistry of the starting material. As for SnI reactions, since the step required for initiation of these reactions involves formation of a planar species, incoming nucleophiles have equal access to both sides of the reactive carbocation. As shown in Scheme 5.7, this results in complete elimination of... 

Correlation of three-dimentional structure and mechanism for heme-containing oxygenases and peroxidases 01MI37. 

RJ Poljak, LM Amzel, BL Chen, RP Phizackerley, F Saul. The three-dimentional structure of the fab fragment of a human myeloma immunoglobulin at 2.0-angstrom resolution. Proc Natl Acad Sci USA 71 3440-3444, 1974. 

Several crude lipase preparations are available from the yeasts Candida lipolytica, C. antarctica (CAL), and C. rugosa (CRL, syn. C. cylindracea). The latter enzyme, the three-dimentional structure of which has been resolved by X-ray analysis [333], has been frequently used for the resolution of esters of secondary alcohols [401-406] and, to a lesser extent, for the resolution of a-substituted carboxylates [407,408]. The CRL preparations from several commercial sources which contain up to 16% of protein [409] differ to some extent in their activity but their selectivity is very similar [410]. As CRL is able to accommodate relatively bulky esters in its active site, it is the lipase of choice for the selective hydrolysis of esters of cyclic secondary alcohols. To illustrate this point, some representative examples are given below. 

Tetraethylene glycol dimethacrylate is a crosslinking agent of acrylic resins, employed to optimize the dilution of high-viscosity monomers and to link together the macromolecules costituting the polymer, to make their three-dimentional structure more rigid. Occupational dermatitis was reported in a dental technician. 

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