TY  - JOUR
AU  - Filipić, Brankica
AU  - Nikolić, Katarina
AU  - Filipić, Slavica
AU  - Jovčić, Branko
AU  - Agbaba, Danica
AU  - Antić-Stanković, Jelena
AU  - Kojić, Milan
AU  - Golić, Nataša
PY  - 2014
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/740
UR  - http://intor.torlakinstitut.com/handle/123456789/838
AB  - The CmbT substrate specificity and its role as a proton motive force-driven drug efflux pump at a molecular level were investigated in the study. In that order, 3D-quantitative structure-activity relationship (3D-QSAR) study was applied for selection of molecular determinants of multidrug recognition by CmbT. CmbT multidrug resistance protein of Lactococcus lactis contributes to extruding the structurally, chemically, and pharmacologically diverse range of substrates out of bacterial cells. This function of CmbT may result in the failure of antibiotic therapy. Homology model of CmbT protein was constructed and further opthnized. The 3D-QSAR model predictive potential was proved by use of leave-one-out cross validation Of the training set (Q(2): 0.69, R-observd(2) (vs).(Predicted) : 0.918, RMSEE: 0.193) and verification set (R-Observed vs predicted(2) : 0.704, RMSEP: 0.289). The results obtained in this study showed that high CmbT affinities to ethidium, sulbactam, and sulfathiazole could be related to the absence of significant unfavourable interactions. In contrast, the presence of specific unfavourable interaction between two hydrogen bond donor groups in bacitracin, apramycin, novobiocin, vancomycin, kanamycin, gentamycin, and tobramycin is found to be the main reason for their lower CmbT affinities. In addition, membrane position of the CmbT binding site and positive correlation between substrates lipophilicity (log D-PH so) and CmbT affinity strongly indicates that CmbT recognizes its substrates within the membrane.
PB  - Elsevier Science Bv, Amsterdam
T2  - Journal of the Taiwan Institute of Chemical Engineers
T1  - Identifying the CmbT substrates specificity by using a quantitative structure-activity relationship (QSAR) study
EP  - 771
IS  - 3
SP  - 764
VL  - 45
DO  - 10.1016/j.jtice.2013.09.033
ER  - 

@article{
author = "Filipić, Brankica and Nikolić, Katarina and Filipić, Slavica and Jovčić, Branko and Agbaba, Danica and Antić-Stanković, Jelena and Kojić, Milan and Golić, Nataša",
year = "2014",
abstract = "The CmbT substrate specificity and its role as a proton motive force-driven drug efflux pump at a molecular level were investigated in the study. In that order, 3D-quantitative structure-activity relationship (3D-QSAR) study was applied for selection of molecular determinants of multidrug recognition by CmbT. CmbT multidrug resistance protein of Lactococcus lactis contributes to extruding the structurally, chemically, and pharmacologically diverse range of substrates out of bacterial cells. This function of CmbT may result in the failure of antibiotic therapy. Homology model of CmbT protein was constructed and further opthnized. The 3D-QSAR model predictive potential was proved by use of leave-one-out cross validation Of the training set (Q(2): 0.69, R-observd(2) (vs).(Predicted) : 0.918, RMSEE: 0.193) and verification set (R-Observed vs predicted(2) : 0.704, RMSEP: 0.289). The results obtained in this study showed that high CmbT affinities to ethidium, sulbactam, and sulfathiazole could be related to the absence of significant unfavourable interactions. In contrast, the presence of specific unfavourable interaction between two hydrogen bond donor groups in bacitracin, apramycin, novobiocin, vancomycin, kanamycin, gentamycin, and tobramycin is found to be the main reason for their lower CmbT affinities. In addition, membrane position of the CmbT binding site and positive correlation between substrates lipophilicity (log D-PH so) and CmbT affinity strongly indicates that CmbT recognizes its substrates within the membrane.",
publisher = "Elsevier Science Bv, Amsterdam",
journal = "Journal of the Taiwan Institute of Chemical Engineers",
title = "Identifying the CmbT substrates specificity by using a quantitative structure-activity relationship (QSAR) study",
pages = "771-764",
number = "3",
volume = "45",
doi = "10.1016/j.jtice.2013.09.033"
}

Filipić, B., Nikolić, K., Filipić, S., Jovčić, B., Agbaba, D., Antić-Stanković, J., Kojić, M.,& Golić, N.. (2014). Identifying the CmbT substrates specificity by using a quantitative structure-activity relationship (QSAR) study. in Journal of the Taiwan Institute of Chemical Engineers
Elsevier Science Bv, Amsterdam., 45(3), 764-771.
https://doi.org/10.1016/j.jtice.2013.09.033

Filipić B, Nikolić K, Filipić S, Jovčić B, Agbaba D, Antić-Stanković J, Kojić M, Golić N. Identifying the CmbT substrates specificity by using a quantitative structure-activity relationship (QSAR) study. in Journal of the Taiwan Institute of Chemical Engineers. 2014;45(3):764-771.
doi:10.1016/j.jtice.2013.09.033 .

Filipić, Brankica, Nikolić, Katarina, Filipić, Slavica, Jovčić, Branko, Agbaba, Danica, Antić-Stanković, Jelena, Kojić, Milan, Golić, Nataša, "Identifying the CmbT substrates specificity by using a quantitative structure-activity relationship (QSAR) study" in Journal of the Taiwan Institute of Chemical Engineers, 45, no. 3 (2014):764-771,
https://doi.org/10.1016/j.jtice.2013.09.033 . .

TY  - JOUR
AU  - Filipić, Brankica
AU  - Golić, Nataša
AU  - Jovčić, Branko
AU  - Tolinački, Maja
AU  - Bay, Denice C.
AU  - Turner, Raymond J.
AU  - Antić-Stanković, Jelena
AU  - Kojić, Milan
AU  - Topisirović, Ljubiša
PY  - 2013
UR  - https://imagine.imgge.bg.ac.rs/handle/123456789/618
UR  - http://intor.torlakinstitut.com/handle/123456789/831
AB  - Functional characterization of the multidrug resistance CmbT transporter was performed in Lactococcus lactis. The cmbT gene is predicted to encode an efflux protein homologous to the multidrug resistance major facilitator superfamily. The cmbT gene (1377 bp) was cloned and overexpressed in L. lactis NZ9000. Results from cell growth studies revealed that the CmbT protein has an effect on host cell resistance to lincomycin, cholate, sulbactam, ethidium bromide, Hoechst 33342, sulfadiazine, streptomycin, rifampicin, puromycin and sulfametoxazole. Moreover, in vivo transport assays showed that overexpressed CmbT-mediated extrusion of ethidium bromide and Hoechst 33342 was higher than in the control L. lactis NZ9000 strain. CmbT-mediated extrusion of Hoechst 33342 was inhibited by the ionophores nigericin and valinomycin known to dissipate proton motive force. This indicates that CmbT-mediated extrusion is based on a drug-proton antiport mechanism. Taking together results obtained in this study, it can be concluded that CmbT is a novel major facilitator multidrug resistance transporter candidate in L. lactis, with a possible signaling role in sulfur metabolism.
PB  - Elsevier, Amsterdam
T2  - Research in Microbiology
T1  - The cmbT gene encodes a novel major facilitator multidrug resistance transporter in Lactococcus lactis
EP  - 54
IS  - 1
SP  - 46
VL  - 164
DO  - 10.1016/j.resmic.2012.09.003
ER  - 

@article{
author = "Filipić, Brankica and Golić, Nataša and Jovčić, Branko and Tolinački, Maja and Bay, Denice C. and Turner, Raymond J. and Antić-Stanković, Jelena and Kojić, Milan and Topisirović, Ljubiša",
year = "2013",
abstract = "Functional characterization of the multidrug resistance CmbT transporter was performed in Lactococcus lactis. The cmbT gene is predicted to encode an efflux protein homologous to the multidrug resistance major facilitator superfamily. The cmbT gene (1377 bp) was cloned and overexpressed in L. lactis NZ9000. Results from cell growth studies revealed that the CmbT protein has an effect on host cell resistance to lincomycin, cholate, sulbactam, ethidium bromide, Hoechst 33342, sulfadiazine, streptomycin, rifampicin, puromycin and sulfametoxazole. Moreover, in vivo transport assays showed that overexpressed CmbT-mediated extrusion of ethidium bromide and Hoechst 33342 was higher than in the control L. lactis NZ9000 strain. CmbT-mediated extrusion of Hoechst 33342 was inhibited by the ionophores nigericin and valinomycin known to dissipate proton motive force. This indicates that CmbT-mediated extrusion is based on a drug-proton antiport mechanism. Taking together results obtained in this study, it can be concluded that CmbT is a novel major facilitator multidrug resistance transporter candidate in L. lactis, with a possible signaling role in sulfur metabolism.",
publisher = "Elsevier, Amsterdam",
journal = "Research in Microbiology",
title = "The cmbT gene encodes a novel major facilitator multidrug resistance transporter in Lactococcus lactis",
pages = "54-46",
number = "1",
volume = "164",
doi = "10.1016/j.resmic.2012.09.003"
}

Filipić, B., Golić, N., Jovčić, B., Tolinački, M., Bay, D. C., Turner, R. J., Antić-Stanković, J., Kojić, M.,& Topisirović, L.. (2013). The cmbT gene encodes a novel major facilitator multidrug resistance transporter in Lactococcus lactis. in Research in Microbiology
Elsevier, Amsterdam., 164(1), 46-54.
https://doi.org/10.1016/j.resmic.2012.09.003

Filipić B, Golić N, Jovčić B, Tolinački M, Bay DC, Turner RJ, Antić-Stanković J, Kojić M, Topisirović L. The cmbT gene encodes a novel major facilitator multidrug resistance transporter in Lactococcus lactis. in Research in Microbiology. 2013;164(1):46-54.
doi:10.1016/j.resmic.2012.09.003 .

Filipić, Brankica, Golić, Nataša, Jovčić, Branko, Tolinački, Maja, Bay, Denice C., Turner, Raymond J., Antić-Stanković, Jelena, Kojić, Milan, Topisirović, Ljubiša, "The cmbT gene encodes a novel major facilitator multidrug resistance transporter in Lactococcus lactis" in Research in Microbiology, 164, no. 1 (2013):46-54,
https://doi.org/10.1016/j.resmic.2012.09.003 . .