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A structural characterization of the isoniazid Mycobacterium tuberculosis drug target, Rv2971, in its unliganded form.

ABSTRACT: 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 Mycobacterium tuberculosis, 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.

SUBMITTER: Shahine A

PROVIDER: S-EPMC4014321 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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A structural characterization of the isoniazid Mycobacterium tuberculosis drug target, Rv2971, in its unliganded form.

Shahine Adam A Prasetyoputri Anggia A Rossjohn Jamie J Beddoe Travis T

Acta crystallographica. Section F, Structural biology communications 20140417 Pt 5

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 Mycobacterium tuberculosis, 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 ...[more]

PMID: 24817712

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