Lysozyme catalysis

Schindler, M., Ascaf, Y., Sharon, N., and Chipman, D. M. Mechanism of lysozyme catalysis role of ground-state strain in subsite D in hen egg and human lysozymes. Biochemistry 16, 423-431 (1977). 

The Lysozyme Mechanism Involves General Acid-Base Catalysis... 

On the basis of the above, the rate acceleration afforded by lysozyme appears to be due to (a) general acid catalysis by Glu (b) distortion of the sugar ring at the D site, which may stabilize the carbonium ion and the transition state) and (c) electrostatic stabilization of the carbonium ion by nearby Asp. The overall for lysozyme is about 0.5/sec, which is quite slow (Table... 

GENERAL ACID CATALYSIS AND ELECTROSTATIC STABILIZATION IN THE CATALYTIC REACTION OF LYSOZYME... 

Hen egg-white lysozyme catalyzes the hydrolysis of various oligosaccharides, especially those of bacterial cell walls. The elucidation of the X-ray structure of this enzyme by David Phillips and co-workers (Ref. 1) provided the first glimpse of the structure of an enzyme-active site. The determination of the structure of this enzyme with trisaccharide competitive inhibitors and biochemical studies led to a detailed model for lysozyme and its hexa N-acetyl glucoseamine (hexa-NAG) substrate (Fig. 6.1). These studies identified the C-O bond between the D and E residues of the substrate as the bond which is being specifically cleaved by the enzyme and located the residues Glu 37 and Asp 52 as the major catalytic residues. The initial structural studies led to various proposals of how catalysis might take place. Here we consider these proposals and show how to examine their validity by computer modeling approaches. 

The commonly accepted mechanism for the catalytic reaction of lysozyme is the so-called general acid catalysis mechanism. 

In order to really assess the magnitude of the electrostatic effect in lysozyme on a microscopic level it is important to simulate the actual assumed chemical process. This can be done by describing the general acid catalysis reaction in terms of the following resonance structures ... 

For what is probably the earliest microscopic calculations of thermodynamic cycles in proteins see Ref. 12, that reported a PDLD study of the pKtt s of some groups in lysozyme. The use of FEP approaches for studies of proteins is more recent and early studies of catalysis and binding were reported in Refs. 11, 12, and 13 of Chapter 4. 

Carbon atom, 4. See also Atomic orbitals Carbon dioxide hydration, 197-199. See also Carbonic anhydrase Carbonic anhydrase, 197-199,200 Carbonium ion transition state, 154, 159 Carboxypeptidase A, 204-205 Catalysis, general acid, 153,164,169 in carboxypeptidase A, 204-205 free energy surfaces for, 160, 161 in lysozyme, 154... 

Highly-efficient general acid catalysis of acetal hydrolysis is involved in the reactions of glycosidase enzymes such as lysozyme (Dunn and Bruice, 1973)... 

General acid catalysis by glutamic acid-35 represents at present the mechanism for lysozyme best able to explain the kinetic and structural data. For it to occur, however, distortion of the hexose ring in subsite D to a half-chair must take place so that relief of strain in the transition state will make bond breaking sufficiently easy. A question that must be answered for this picture to be tenable is whether relief of strain can so greatly facilitate bond breaking when the carbonium ion is a glycosyl ion [see also the discussion in Fife (1972) and Atkinson and Bruice (1974)]. 

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