National Center for
2NTN: Crystal Structure Of Maba-c60v/g139a/s144l
Lack of dynamics in the MabA active site kills the enzyme activity: practical consequences for drug-design studies
Acta Crystallogr. D Biol. Crystallogr. (2007) 63 p.923-925
The MabA protein from Mycobacterium tuberculosis is a validated drug target. Previous structural studies of this protein showed dynamic behaviour in the catalytic site and described motion between an open 'active' holo form (with NADP) and a closed 'inactive' apo form (without NADP). Here, a mutation (G139A) is reported that leads to complete protein inactivation and freezes the catalytic site into its closed form, even in the presence of the cofactor. This observation suggests a new way to develop anti-MabA drugs via protein stabilization of the 'inactive' form.