TY - GEN
T1 - β laktamaz - li̇gand etki̇leşi̇mi̇ni̇n di̇nami̇k anali̇zi̇
AU - Kanlikiliçer, Pinar
AU - Büdeyri, Nilay
AU - Akbulut, Berna Sariyar
AU - Hortaçsu, Amable
AU - Özkirimli Ölmez, Elif
N1 - Copyright:
Copyright 2009 Elsevier B.V., All rights reserved.
PY - 2009
Y1 - 2009
N2 - β-lactam antibiotics are the most commonly used antibiotics which cause bacterial cell lysis by inhibiting the enzyme responsible for the cell wall synthesis. Production of β-lactamase enzyme, which catalyzes the hydrolysis of β-lactam ring of β-lactam antibiotics is the most common mechanism of bacterial resistance. β-Lactamase Inhibitory Protein (BLIP), is an effective inhibitor of class A β-lactamases such as TEM-1 and SHV-1. TEM-1 and SHV-1 are the most commonly found β-lactamases and they are responsible for the resistance to β-lactam antibiotics of various pathogenic bacteria. In an effort to elucidate the mechanism of β-lactamase inhibiton by BLIP and to make predictions of binding affinity between these molecules, Molecular Dynamics (MD) simulations were performed on TEM-1 and SHV-1 bound to BLIP and BLIP based peptides. Asp49 residue which is known to play a critical role on binding on BLIP was mutated to Alanine to determine the contribution of this residue to binding. Binding free energy of the TEM-1 and SHV-1 bound BLIP, mutant BLIP (D49A) complexes were estimated by the molecular mechanics Poisson Boltzmann Surface Area method (MM-PBSA). Free energy of binding calculations show that the mutation on D49 causes a decrease in binding affinity for both TEM-1 and SHV-1 β-lactamase.
AB - β-lactam antibiotics are the most commonly used antibiotics which cause bacterial cell lysis by inhibiting the enzyme responsible for the cell wall synthesis. Production of β-lactamase enzyme, which catalyzes the hydrolysis of β-lactam ring of β-lactam antibiotics is the most common mechanism of bacterial resistance. β-Lactamase Inhibitory Protein (BLIP), is an effective inhibitor of class A β-lactamases such as TEM-1 and SHV-1. TEM-1 and SHV-1 are the most commonly found β-lactamases and they are responsible for the resistance to β-lactam antibiotics of various pathogenic bacteria. In an effort to elucidate the mechanism of β-lactamase inhibiton by BLIP and to make predictions of binding affinity between these molecules, Molecular Dynamics (MD) simulations were performed on TEM-1 and SHV-1 bound to BLIP and BLIP based peptides. Asp49 residue which is known to play a critical role on binding on BLIP was mutated to Alanine to determine the contribution of this residue to binding. Binding free energy of the TEM-1 and SHV-1 bound BLIP, mutant BLIP (D49A) complexes were estimated by the molecular mechanics Poisson Boltzmann Surface Area method (MM-PBSA). Free energy of binding calculations show that the mutation on D49 causes a decrease in binding affinity for both TEM-1 and SHV-1 β-lactamase.
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U2 - 10.1109/BIYOMUT.2009.5130306
DO - 10.1109/BIYOMUT.2009.5130306
M3 - Conference contribution
AN - SCOPUS:70350234795
SN - 9781424436064
T3 - Proceedings of 2009 14th National Biomedical Engineering Meeting, BIYOMUT 2009
BT - Proceedings of 2009 14th National Biomedical Engineering Meeting, BIYOMUT 2009
T2 - 2009 14th National Biomedical Engineering Meeting, BIYOMUT 2009
Y2 - 20 May 2009 through 22 May 2009
ER -