TY - JOUR
T1 - Simulation of the cavity-binding site of three bacterial multicopper oxidases upon complex stabilization
T2 - Interactional profile and electron transference pathways
AU - Bello, Martiniano
AU - Correa-Basurto, Jose
AU - Rudiño-Piñera, Enrique
N1 - Funding Information:
This work was supported in part by DGAPA, UNAM [PAPIIT, IN 204611, CONACyT [Grants 102370, 128156 and 132353] and ICyTDF (PIRIVE09-9, COFAA-SIP/IPN). MB acknowledges the Program of Postdoctoral Scholarships from DGAPA (UNAM) and CONACyT. This work was carried out using a KanBalam supercomputer, provided by DGTIC, UNAM.
PY - 2014/8/3
Y1 - 2014/8/3
N2 - Previous studies have shown that multicopper oxidases (MCOs) oxidize organic and inorganic compounds through oxidation-reduction reactions in which three structurally and functionally arranged copper centers coordinate the uptake of an electron from a reduced substrate. Structural comparisons among three bacterial MCOs, with high structural homology and available three-dimensional information, reveal that the primary structural differences between these MCOs are located near the mononuclear copper center (T1Cu), where substrate oxidation occurs, as opposed to where the reduction of oxygen to water occurs at the trinuclear center. Nevertheless, this substrate oxidation is achieved through an outer-sphere electron transfer mechanism that does not generate a stable substrate-enzyme complex. In this study, MCOs from Thermus thermophilus (Tth-MCO), Bacillus subtilis (CotA), and Escherichia coli (CueO), which have been previously determined through X-ray crystallography, were used as models to analyze the binding modes of these MCOs to three organic molecules, with specific interest in the substrate-binding site. The binding mode of the electron-donor molecule to the electron transfer binding site was primarily attributed to hydrophobic contacts, which likely play an important role in the determination of substrate specificity. Some complexes generated in this study showed an electron donor molecule conformation in which an electron could be directly transferred to the histidines coordinating T1Cu, while for others additional electron transference pathways were also possible through the participation of charged residues during electron transfer.
AB - Previous studies have shown that multicopper oxidases (MCOs) oxidize organic and inorganic compounds through oxidation-reduction reactions in which three structurally and functionally arranged copper centers coordinate the uptake of an electron from a reduced substrate. Structural comparisons among three bacterial MCOs, with high structural homology and available three-dimensional information, reveal that the primary structural differences between these MCOs are located near the mononuclear copper center (T1Cu), where substrate oxidation occurs, as opposed to where the reduction of oxygen to water occurs at the trinuclear center. Nevertheless, this substrate oxidation is achieved through an outer-sphere electron transfer mechanism that does not generate a stable substrate-enzyme complex. In this study, MCOs from Thermus thermophilus (Tth-MCO), Bacillus subtilis (CotA), and Escherichia coli (CueO), which have been previously determined through X-ray crystallography, were used as models to analyze the binding modes of these MCOs to three organic molecules, with specific interest in the substrate-binding site. The binding mode of the electron-donor molecule to the electron transfer binding site was primarily attributed to hydrophobic contacts, which likely play an important role in the determination of substrate specificity. Some complexes generated in this study showed an electron donor molecule conformation in which an electron could be directly transferred to the histidines coordinating T1Cu, while for others additional electron transference pathways were also possible through the participation of charged residues during electron transfer.
KW - dynamic Simulations
KW - electron transfer mechanism
KW - multicopper oxidases
KW - protein ligand interactions
KW - transient complexes
UR - http://www.scopus.com/inward/record.url?scp=84899646478&partnerID=8YFLogxK
U2 - 10.1080/07391102.2013.817954
DO - 10.1080/07391102.2013.817954
M3 - Artículo
C2 - 23859715
SN - 0739-1102
VL - 32
SP - 1303
EP - 1317
JO - Journal of Biomolecular Structure and Dynamics
JF - Journal of Biomolecular Structure and Dynamics
IS - 8
ER -