Title:Structure-and-Mechanism-Based Design and Discovery of Type II Mycobacterium Tuberculosis Dehydroquinate Dehydratase Inhibitors
Volume: 14
Issue: 1
Author(s): Yuan Yao and Li Ze-Sheng
Affiliation:
Keywords:
Binding affinity, dehydroquinate dehydratase, drug design and discovery, inhibitor, Mycobacterium tuberculosis,
tuberculosis.
Abstract: Mycobacterium tuberculosis is the causative agent of tuberculosis, a lethal infection disease that attacks the
lungs. Now it becomes the major global health risk because of very long latent period, the persistent increase of new
cases, and the emergence of multidrug-resistant and extensively drug-resistant strains. Therefore, there is an urgent need
for the development of new, safe and more efficient tuberculosis drugs. The shikimate pathway has been considered as the
attractive drug target due to its essentiality in algae, higher plants, bacteria, and fungi, but absence from mammals. In this
review, we focus on the recent development of a wide variety of inhibitors of type II Mycobacterium tuberculosis dehydroquinate
dehydratase, the third enzyme of this pathway. The structural and mechanistic features of the enzyme for the
design and discovery of the inhibitors have been described. The key factors on the structure, binding, and affinity of the
inhibitors have been also highlighted. This may direct the further development of type II Mycobacterium tuberculosis dehydroquinate
dehydratase inhibitors as potent tuberculosis drugs.
