Open AccessStructural study and thermodynamic characterization of inhibitor binding to lumazine synthase from Bacillus anthracis
Author(s) -
Morgunova Ekaterina,
Illarionov Boris,
Saller Sabine,
Popov Aleksander,
Sambaiah Thota,
Bacher Adelbert,
Cushman Mark,
Fischer Markus,
Ladenstein Rudolf
Publication year - 2010
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
ISSN - 1399-0047
DOI - 10.1107/s0907444910029690
Subject(s) - bacillus anthracis , isothermal titration calorimetry , active site , chemistry , stereochemistry , dissociation constant , enzyme , binding site , atp synthase , biochemistry , biology , receptor , bacteria , genetics
The crystal structure of lumazine synthase from Bacillus anthracis was solved by molecular replacement and refined to R cryst = 23.7% ( R free = 28.4%) at a resolution of 3.5 Å. The structure reveals the icosahedral symmetry of the enzyme and specific features of the active site that are unique in comparison with previously determined orthologues. The application of isothermal titration calorimetry in combination with enzyme kinetics showed that three designed pyrimidine derivatives bind to lumazine synthase with micromolar dissociation constants and competitively inhibit the catalytic reaction. Structure‐based modelling suggested the binding modes of the inhibitors in the active site and allowed an estimation of the possible contacts formed upon binding. The results provide a structural framework for the design of antibiotics active against B. anthracis .