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The three-dimensional structure of VIM-31-a metallo-beta-lactamase from Enterobacter cloacae in its native and oxidized form

 
: Kupper, M.B.; Herzog, K.; Bennink, S.; Schlomer, P.; Bogaerts, P.; Glupczynski, Y.; Fischer, R.; Bebrone, C.; Hoffmann, K.M.

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FEBS journal 282 (2015), No.12, pp.2352-2360
ISSN: 1742-464X
ISSN: 1432-1033
ISSN: 1742-4658
English
Journal Article
Fraunhofer IME ()

Abstract
The metallo-beta-lactamase VIM-31 differs from VIM-2 by only two Tyr224-His and His252Arg substitutions. Located close to the active site, the Tyr224His substitution is also present in VIM-1, VIM-4, VIM-7 and VIM-12. The VIM-31 variant was reported in 2012 from Enterobacter cloacae and kinetically characterized. It exhibits globally lower catalytic efficiencies than VIM-2. In the present study, we report the three-dimensional structures of VIM-31 in its native (reduced) and oxidized forms. The so-called 'flapping-loop' (loop 1) and loop 3 of VIM-31 were not positioned as in VIM-2 but instead were closer to the active site as in VIM-4, resulting in a narrower active site in VIM-31. Also, the presence of His224 in VIM-31 disrupts hydrogen-bonding networks close to the active site. Moreover, a third zinc-binding site, which also exists in VIM-2 structures, could be identified as a structural explanation for the decreased activity of VIM-MBLs at high zinc concentrations.

: http://publica.fraunhofer.de/documents/N-369685.html