Beta-N-acetylhexosaminidase: a target for the design of antifungal agents

Pharmacology & Therapeutics
M HorschD M Rast

Abstract

This review provides biochemical, analytical, and biological background information relating to beta-N-acetylhexosaminidase (HexNAc'ase; EC 3.2.1.52) as an emerging target for the design of low-molecular-weight antifungals. The article includes the following: (1) a biochemical description of HexNAc'ase (reaction catalyzed, nomenclature, and mechanism of action) that sets it apart from other, similar enzymes; (2) an overview and a critical evaluation of methods to assay the enzyme, including in crude extracts (photo- and fluorometric procedures with model substrates; HPLC/pulsed amperometric detection of N-acetylglucosamine and chito-oligomers; end-point vs. rate measurements); (3) a summary of some general characteristics of HexNAc'ases from fungi and organisms of other types (Km values, substrate preference, and glycoconjugation); (4) an hypothesis of a specific target function of wall-associated HexNAc'ase (a component of the assembly of surface-located enzymes effecting a continuous turnover and remodelling of the wall fabric through its combined hydrolytic and transglycosylating activities, and a mediator enzyme acting in concert with chitinase and chitin synthase to provide for the controlled lysis and synthesis of chitin ...Continue Reading

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