2NTN

Crystal structure of MabA-C60V/G139A/S144L

Summary for 2NTN

• Entry DOI: 10.2210/pdb2ntn/pdb
• Related: 1UZL 1UZM 1UZN
• Descriptor: 3-oxoacyl-[acyl-carrier-protein] reductase (2 entities in total)
• Functional Keywords: beta-ketoacyl acp reductase, oxidoreductase, inactive, sdr
• Biological source: Mycobacterium tuberculosis H37Rv
• Total number of polymer chains: 2
• Total formula weight: 55867.34

Authors

Poncet-Montange, G.,Ducasse-Cabanot, S.,Quemard, A.,Labesse, G.,Cohen-Gonsaud, M. (deposition date: 2006-11-08, release date: 2006-11-21, Last modification date: 2023-10-25)

Primary citation

Poncet-Montange, G.,Ducasse-Cabanot, S.,Quemard, A.,Labesse, G.,Cohen-Gonsaud, M.
Lack of dynamics in the MabA active site kills the enzyme activity: practical consequences for drug-design studies
ACTA CRYSTALLOGR.,SECT.D, 63:923-925, 2007

PubMed Abstract: 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.

PubMed: 17642518
DOI: 10.1107/S0907444907024158

Experimental method

X-RAY DIFFRACTION (2.3 Å)