Conformational changes of nucleotide-bindings site for the antibiotics development against D-ala- D-ala ligase from Acinetobactor baumannii

5^th International Conference on Medicinal Chemistry & Computer Aided Drug Designing and Drug Delivery

December 05-07, 2016 Phoenix, USA

Lin-Woo Kang

Konkuk University, South Korea

Posters & Accepted Abstracts: Med chem

Abstract :

Acinetobacter baumannii, which is emerging as a multidrug-resistant nosocomial pathogen, causes a number of diseases, including pneumonia, bacteremia, meningitis and skin infections. With ATP hydrolysis, the d-alanine-d-alanine ligase (DDL) catalyzes the synthesis of d-alanyl-d-alanine, which is an essential component of bacterial peptidoglycan. Structural studies showed the flexible conformational changes in the ATP-binding site, more specifically both the hydrophobic nucleotide base binding site and the hydrophilic triphosphate binding site with the movement of the central domain and serine-loop. The central domain of AbDDL (DDl from Acinetobacter baumannii) can have an ensemble of the open and closed conformations before the binding of substrate ATP. In other DDL structures from Xanthomonas oryzae pv. oryzae and Yersinia pestis, the serineloop and the �?-loop showed flexible conformations, especially the serine-loop is mainly responsible for the conformational change in substrate nucleotide phosphates. Currently, computer-aided drug design method has been actively and efficiently used. The detail catalytic mechanism and structure information will be helpful to apply the CADD method in drug discovery.

Biography :

Lin-Woo Kang has completed his PhD at Johns Hopkins University School of Medicine and Post-doctoral studies from Stanford University School of Medicine. He is a Professor at Konkuk University. He has published more than 75 papers in reputed journals in the field of Structural Biology.

Email: lkang@konkuk.ac.kr