Structure and Function of the LmbE-like Superfamily

Biomolecules

Shane Viars¹  Jason Valentine¹ 

[1]Department of Pharmaceutical Sciences, Appalachian College of Pharmacy, Oakwood, VA 24631, USA

关键词: metallohydrolase;    metal-dependent deacetylase;    zinc;    LmbE-like;    PIG-L;    MshB;    teicoplanin;    BshB;    mycothiol-conjugate amidase;    bacillithiol-conjugate amidase;   

DOI  :  10.3390/biom4020527

来源: mdpi

【 摘 要 】

The LmbE-like superfamily is comprised of a series of enzymes that use a single catalytic metal ion to catalyze the hydrolysis of various substrates. These substrates are often key metabolites for eukaryotes and prokaryotes, which makes the LmbE-like enzymes important targets for drug development. Herein we review the structure and function of the LmbE-like proteins identified to date. While this is the newest superfamily of metallohydrolases, a growing number of functionally interesting proteins from this superfamily have been characterized. Available crystal structures of LmbE-like proteins reveal a Rossmann fold similar to lactate dehydrogenase, which represented a novel fold for (zinc) metallohydrolases at the time the initial structure was solved. The structural diversity of the N-acetylglucosamine containing substrates affords functional diversity for the LmbE-like enzyme superfamily. The majority of enzymes identified to date are metal-dependent deacetylases that catalyze the hydrolysis of a N-acetylglucosamine moiety on substrate using a combination of amino acid side chains and a single bound metal ion, predominantly zinc. The catalytic zinc is coordinated to proteins via His₂-Asp-solvent binding site. Additionally, studies indicate that protein dynamics play important roles in regulating access to the active site and facilitating catalysis for at least two members of this protein superfamily.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.