Staphylococcus aureus FabI: Inhibition, Substrate Recognition, and Potential Implications for In Vivo Essentiality

Type II Fatty Acid Synthesis Is Essential for the Replication of Chlamydia trachomatis

“…3D). NADPH was Ͼ1000-fold less efficient than NADH in supporting the reaction, consistent with CtFabI preferring NADH like most bacterial FabIs, with the sole exception of SaFabI (30,34). The k cat of CtFabI with NADH and crotonyl-ACP was 15.6 Ϯ 0.05 min Ϫ1 , which is similar in velocity to other characterized FabI enzymes (35).…”

Structural Basis for the Recognition of Mycolic Acid Precursors by KasA, a Condensing Enzyme and Drug Target from Mycobacterium Tuberculosis

“…This is nicely illustrated by recent studies concerning the induced fit binding of peptide deformylase and enoyl-ACP reductase inhibitors (20,49,61). For instance, the picomolar affinity of diphenyl ether enoyl-ACP reductase inhibitors can be related to their capability to mimic the transition state of the catalyzed reaction and to trigger the correlated ordering of a flexible loop (20,61). In the present study, we reveal snapshots of the dynamic process that is involved in the recognition of very long chain fatty acyl substrates by the drug target KasA.…”

“…In light of the fact that the free energy of the transition state along the reaction coordinate has to be lowered efficiently, it is not very surprising that the dynamics of substrate binding and catalysis are also reflected in the inhibition of enzymes (49,59,60). This is nicely illustrated by recent studies concerning the induced fit binding of peptide deformylase and enoyl-ACP reductase inhibitors (20,49,61). For instance, the picomolar affinity of diphenyl ether enoyl-ACP reductase inhibitors can be related to their capability to mimic the transition state of the catalyzed reaction and to trigger the correlated ordering of a flexible loop (20,61).…”

Computer-aided discovery of antimicrobial agents as potential enoyl acyl carrier protein reductase inhibitors

“…The saFabI crystal structure was obtained from the protein data bank (http://www.rcsb.org/), PDB: 4ALK [8]. All solvent molecules were eliminated prior to protein preparation.…”