A structural characterization of the isoniazid Mycobacterium tuberculosis drug target, Rv2971, in its unliganded form. Issue 5 (1st May 2014)

• Record Type: Journal Article
• Authors: Shahine, Adam; Prasetyoputri, Anggia; Rossjohn, Jamie; Beddoe, Travis
• Is Part Of: Acta crystallographica. Volume 70:Issue 5(2014:May)
• Page Start: 572
• Page End: 577
• Publication Date: 2014-05-01
• Subjects: Crystallography -- Periodicals; Crystals -- Periodicals; 548
• DOI: 10.1107/S2053230X14007158
• Languages: English
• ISSNs: 2053-230X

Abstract

<abstract abstract-type="main" xml:lang="en"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Aldo‐keto reductases (AKR) are a large superfamily of NADPH‐dependent oxidoreductases and play a role in detoxification of toxic metabolites. Rv2971, an AKR in <italic>Mycobacterium tuberculosis</italic>, has recently been identified as a target of isoniazid, a key first‐line drug against tuberculosis. Here, the cloning, expression, purification, crystallization and structural characterization of Rv2971 are described. To gain insight into its function, the crystal structure of Rv2971 was successfully determined to 1.60 Å resolution in its unliganded form. The structure exhibits a TIM‐barrel fold typical of AKRs, revealing structural characteristics essential for function and substrate specificities, allowing a structural comparison between Rv2971 and other mycobacterial AKRs.</p> </abstract>