Other Hydrolases

Figure 16.6 Other hydrolase inhibitors from virtual screening.

Second, esterases have broad (or even very broad) and overlapping substrate specificities. For example, carboxylesterase (EC 3.1.1.1) also catalyzes reactions characteristic of a number of other hydrolases. The discovery that individual isoenzymes of carboxylesterases may be identical to or closely related to acylglycerol lipase, acylcamitine hydrolase, and palmitoyl-CoA hydrolase (see Sect. 2.4.3) has increased the confusion surrounding esterase classification [59], Many esterases are able to hydrolyze amides, thiolesters,... 

Peptide hydrolases (peptidases or proteases, i.e., enzymes hydrolyzing peptide bonds in peptides and proteins, see Chapt. 2) have received particular attention among hydrolases. As already described in Chapt. 2, peptidases are divided into exopeptidases (EC 3.4.11 -19), which cleave one or a few amino acids from the N- or C-terminus, and endopeptidas-es (proteinases, EC 3.4.21-99), which act internally in polypeptide chains [2], The presentation of enzymatic mechanisms of hydrolysis in the following sections will begin with peptidases and continue with other hydrolases such as esterases. 

A critical input in unraveling the catalytic mechanism of epoxide hydrolases has come from the identification of essential residues by a variety of techniques such as analysis of amino acid sequence relationships with other hydrolases, functional studies of site-directed mutated enzymes, and X-ray protein crystallography (e.g., [48][53][68 - 74]). As schematized in Fig. 10.6, the reaction mechanism of microsomal EH and cytosolic EH involves a catalytic triad consisting of a nucleophile, a general base, and a charge relay acid, in close analogy to many other hydrolases (see Chapt. 3). 

Lipases (triacyl glycerol acyl hydrolases, E.C 3.1.1.3) are a unique class of hydrolases for asymmetric synthesis86,87,S9,90e, They are available from fungi, bacteria and mammalians. The lipases most commonly used so far are the commercially supplied pig pancreas lipase (PPL)136, Pseudomonas cepacia lipase (PCL)89,137 and Candida cylindracea lipase (CCL). In most cases only the crude lipases, consisting of a mixture of proteins which may even be other hydrolases, are successfully applied1373. 

S-selectivity toward 1-phenylethanol [35]. Several other hydrolases have also been redesigned by protein engineering to invert or enhance their enantioselectivity [36-40]. 

Hydrolase-catalyzed enantioselective N-acylation is an important tool for the preparation of enantiopure a- and P-aminoacids. It has been observed that the reactions of many amino acid esters with ester acyl donors catalyzed by CALB is sometimes complicated by interesterification reactions. CALA has, however, emerged as a very chemoselective catalyst in favor of N-acylation of P-aminoesters. Some reviews on CALA and other hydrolases as catalysts for N-acylations of aminoesters are available [109, 126, 127]. 

Penicillin and related antibiotics are inactivated by P-lactamases (Box 20-G), some of which resemble serine proteases in forming acyl enzymes with active site serine side chains.656 657 Others are zinc metallogen-zymes.658/659 Amidohydrolases such as asparaginase and glutaminase,660/661 deacetylases,662 and many other hydrolases can also be described as acyltransferases. 

Lysosomes, which contain more than 50 proteases, lipases, glycosidases, and other hydrolases, also play a... 

The four types of nickel-containing enzymes are quite distinct in the coordination sites and catalytic function of the nickel centers. In urease, the nickel appears to be bound to oxygen and nitrogen ligands and appears to remain as Ni(II), a state which favors octahedral or square-planar coordination. The function of nickel in this unique case may be analogous to that of zinc in other hydrolases such as carboxypeptidase. 

Kilbum, D. G., Assouline, Z., Din, N., Gilkes, N. R., Ong, E., Tomme, P., and Warren, R. A. J. 1993. Cellulose binding domains properties and applications. Proceedings of the second TRICEL symposium on Trichoderma Reesei cellulases and other hydrolases. Espoo, Finland. In Suominen, R, and Rainikainen, T. (Eds.), Foundation for Biotechnological and Industrial fermentation Research 8,281-290. 

For the other hydrolases general rules for their enantioselectivity are not available. This does not mean that their enantioselectivities are unknown indeed for many enzymes much knowledge is available, however, less is known about the entire class of enzymes of which these individual, well-researched enzymes are an element. 

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