Molecular symmetry in enzyme function
Beáta G. Vértessy
Department of Applied Biotechnology and Food Sciences, Faculty of Chemical Engineering and
Bioengineering, Budapest University of Technology and Economics and Inst. Enzymology, Res Ctr
Nat Sci, Hungarian Academy of Sciences [email protected]
Enzymatic action ultimately depends on the creation of a microenvironment to facilitate
chemical reaction. Active site architecture of many enzymes reflects a built-in symmetry –
this characteristics is most evidently observed in dimeric enzymes with two identical active
sites. Trimeric organization offers another type of symmetry also present in a few enzyme
families. This talk will focus on the trimeric dUTPases that provides an eminent example of
symmetrical active sites located at subunit clefts. The physiological function of dUTPases is
to preserve genomic integrity. Inhibition of these enzymes is considered to be a highly
promising chemotherapeutic strategy against cancer and infective diseases. In these proteins,
the trimeric organization results in a highly interesting threefold channel within the core of the
trimeric oligomer. The characteristics of the inner channel is different in dUTPases from
diverse evolutionary clades (eg between pro- and eukaryotic dUTPases). These alterations are
suggested to modulate protein stability and enzyme efficiency. The talk will also cover how
these fascinating trimeric enzymes may from macromolecular complexes with other proteins.
References:
[1] Szabó et al, Vértessy BG. Nucleic Acids Res. 2014 42(19):11912-20.
[2] Nagy GN, Leveles I, Vértessy BG. FEBS J. 2014 Sep;281(18):4207-23.
[3]: Barabás et al, Vértessy BG. Nucleic Acids Res. 2013 Dec;41(22):10542-55.
[4] Pécsi I, Szabó JE, Adams SD, Simon I, Sellers JR, Vértessy BG, Tóth J.
Proc Natl Acad Sci U S A. 2011 Aug 30;108(35):14437-42.
[5] Vértessy BG, Tóth J. Acc Chem Res. 2009 Jan 20;42(1):97-106.