Elucidation of the protonation states of the catalytic residues in mtKasA: implications for inhibitor design.

ABSTRACT: KasA (β-ketoacyl ACP synthase I) is involved in the biosynthetic pathway of mycolic acids, an essential component of the cell wall in Mycobacterium tuberculosis. It was shown that KasA is essential for the survival of the pathogen and thus could serve as a new drug target for the treatment of tuberculosis. The active site of KasA was previously characterized by X-ray crystallography. However, questions regarding the protonation state of specific amino acids, the orientation of the histidine groups within the active site, and additional conformers being accessible at ambient temperatures remain open and have to be addressed prior to the design of new inhibitors. We investigate the active site of KasA in this work by means of structural motifs and relative energies. Molecular dynamics (MD) s

SUBMITTER: Lee W 

PROVIDER: S-EPMC4397578 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature