% IMPORTANT: The following is UTF-8 encoded. This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.
@ARTICLE{Sgrignani:201299,
author = {Sgrignani, Jacopo and Magistrato, Alessandra and Dal
Peraro, Matteo and Vila, Alejandro J. and Carloni, Paolo and
Pierattelli, Roberta},
title = {{O}n the active site of mononuclear {B}1 metallo
β-lactamases: a computational study},
journal = {Journal of computer aided molecular design},
volume = {26},
number = {4},
issn = {1573-4951},
address = {Dordrecht [u.a.]},
publisher = {Springer Science + Business Media B.V},
reportid = {FZJ-2015-03604},
pages = {425 - 435},
year = {2012},
abstract = {Metallo-β-lactamases (MβLs) are Zn(II)-based bacterial
enzymes that hydrolyze β-lactam antibiotics, hampering
their beneficial effects. In the most relevant subclass
(B1), X-ray crystallography studies on the enzyme from
Bacillus Cereus point to either two zinc ions in two metal
sites (the so-called ‘3H’ and ‘DCH’ sites) or a
single Zn(II) ion in the 3H site, where the ion is
coordinated by Asp120, Cys221 and His263 residues. However,
spectroscopic studies on the B1 enzyme from B. Cereus in the
mono-zinc form suggested the presence of the Zn(II) ion also
in the DCH site, where it is bound to an aspartate, a
cysteine, a histidine and a water molecule. A structural
model of this enzyme in its DCH mononuclear form, so far
lacking, is therefore required for inhibitor design and
mechanistic studies. By using force field based and mixed
quantum–classical (QM/MM) molecular dynamics (MD)
simulations of the protein in aqueous solution we
constructed such structural model. The geometry and the
H-bond network at the catalytic site of this model, in the
free form and in complex with two common β-lactam drugs, is
compared with experimental and theoretical findings of CphA
and the recently solved crystal structure of new B2 MβL
from Serratia fonticola (Sfh-I). These are MβLs from the B2
subclass, which features an experimentally well established
mono-zinc form, in which the Zn(II) is located in the DCH
site. From our simulations the εεδ and δεδ protomers
emerge as possible DCH mono-zinc reactive species, giving a
novel contribution to the discussion on the MβL reactivity
and to the drug design process.},
cin = {GRS / IAS-5},
ddc = {570},
cid = {I:(DE-Juel1)GRS-20100316 / I:(DE-Juel1)IAS-5-20120330},
pnm = {899 - ohne Topic (POF2-899)},
pid = {G:(DE-HGF)POF2-899},
typ = {PUB:(DE-HGF)16},
UT = {WOS:000303882200005},
pubmed = {pmid:22532071},
doi = {10.1007/s10822-012-9571-0},
url = {https://juser.fz-juelich.de/record/201299},
}