Lysozyme
Lysozyme (EC 3.2.1.17, muramidase, N-acetylmuramide glycanhydrolase; systematic name peptidoglycan N-acetylmuramoylhydrolase) is an antimicrobial enzyme produced by animals that forms part of the innate immune system.
It is a glycoside hydrolase that catalyzes the following process: Peptidoglycan is the major component of gram-positive bacterial cell wall.
C-type lysozymes are closely related to α-lactalbumin in sequence and structure, making them part of the same glycoside hydrolase family 22.
[12] The Phillips mechanism proposed that the enzyme's catalytic power came from both steric strain on the bound substrate and electrostatic stabilization of an oxo-carbenium intermediate.
[14] Thus distortion causing the substrate molecule to adopt a strained conformation similar to that of the transition state will lower the energy barrier of the reaction.
[15] The proposed oxo-carbonium intermediate was speculated to be electrostatically stabilized by aspartate and glutamate residues in the active site by Arieh Warshel in 1978.
By tracing the formation of product (p-nitrophenol), it was discovered that the RDS can change over different temperatures, which was a reason for those contradictory results.
[22] Evidence for the ESI-MS and X-ray structures indicate the existence of covalent intermediate, but primarily rely on using a less active mutant or non-native substrate.
Thus, QM/MM molecular dynamics provides the unique ability to directly investigate the mechanism of wild-type HEWL and native substrate.
[citation needed] Imidazole derivatives can form a charge-transfer complex with some residues (in or outside active center) to achieve a competitive inhibition of lysozyme.
[24]Despite that the muramidase activity of lysozyme has been supposed to play the key role for its antibacterial properties, evidence of its non-enzymatic action was also reported.
[25] The lectin-like ability of lysozyme to recognize bacterial carbohydrate antigen without lytic activity was reported for tetrasaccharide related to lipopolysaccharide of Klebsiella pneumoniae.
[35] Piglets fed with human lysozyme milk can recover from diarrheal disease caused by E. coli faster.
[36][37] Since lysozyme is a natural form of protection from Gram-positive pathogens like Bacillus and Streptococcus,[38] it plays an important role in immunology of infants in human milk feeding.
[40] The first chemical synthesis of a lysozyme protein was attempted by Prof. George W. Kenner and his group at the University of Liverpool in England.
[41] This was finally achieved in 2007 by Thomas Durek in Steve Kent's lab at the University of Chicago who made a synthetic functional lysozyme molecule.
Newly invented strains, containing a helper plasmid (pLysS), constitutively co-express low levels of T7 lysozyme, providing high stringency and consistent expression of the toxic recombinant protein.
[53] The bacteria-killing activity of nasal mucus was demonstrated in 1922 by Alexander Fleming, the discoverer of penicillin, who coined the term "lysozyme".
"[55] Fleming went on to show that an enzymic substance was present in a wide variety of secretions and was capable of rapidly lysing (i.e. dissolving) different bacteria, particularly a yellow "coccus" that he studied".
[60] As a result of Phillips' elucidation of the structure of lysozyme, it was also the first enzyme to have a detailed, specific mechanism suggested for its method of catalytic action.
[61][62][63] This work led Phillips to provide an explanation for how enzymes speed up a chemical reaction in terms of its physical structures.
