2cig

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{{STRUCTURE_2cig| PDB=2cig | SCENE= }}
{{STRUCTURE_2cig| PDB=2cig | SCENE= }}
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'''DIHYDROFOLATE REDUCTASE FROM MYCOBACTERIUM TUBERCULOSIS INHIBITED BY THE ACYCLIC 4R ISOMER OF INH-NADP A DERIVATIVE OF THE PRODRUG ISONIAZID.'''
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===DIHYDROFOLATE REDUCTASE FROM MYCOBACTERIUM TUBERCULOSIS INHIBITED BY THE ACYCLIC 4R ISOMER OF INH-NADP A DERIVATIVE OF THE PRODRUG ISONIAZID.===
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==Overview==
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Isoniazid is a key drug used in the treatment of tuberculosis. Isoniazid is a pro-drug, which, after activation by the katG-encoded catalase peroxidase, reacts nonenzymatically with NAD(+) and NADP(+) to generate several isonicotinoyl adducts of these pyridine nucleotides. One of these, the acyclic 4S isomer of isoniazid-NAD, targets the inhA-encoded enoyl-ACP reductase, an enzyme essential for mycolic acid biosynthesis in Mycobacterium tuberculosis. Here we show that the acyclic 4R isomer of isoniazid-NADP inhibits the M. tuberculosis dihydrofolate reductase (DHFR), an enzyme essential for nucleic acid synthesis. This biologically relevant form of the isoniazid adduct is a subnanomolar bisubstrate inhibitor of M. tuberculosis DHFR. Expression of M. tuberculosis DHFR in Mycobacterium smegmatis mc(2)155 protects cells against growth inhibition by isoniazid by sequestering the drug. Thus, M. tuberculosis DHFR is the first new target for isoniazid identified in the last decade.
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(as it appears on PubMed at http://www.pubmed.gov), where 16648861 is the PubMed ID number.
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{{ABSTRACT_PUBMED_16648861}}
==About this Structure==
==About this Structure==
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[[Category: Reductase]]
[[Category: Reductase]]
[[Category: Tuberculosis]]
[[Category: Tuberculosis]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 04:44:17 2008''

Revision as of 01:44, 28 July 2008

Image:2cig.png

Template:STRUCTURE 2cig

DIHYDROFOLATE REDUCTASE FROM MYCOBACTERIUM TUBERCULOSIS INHIBITED BY THE ACYCLIC 4R ISOMER OF INH-NADP A DERIVATIVE OF THE PRODRUG ISONIAZID.

Template:ABSTRACT PUBMED 16648861

About this Structure

2CIG is a Single protein structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.

Reference

Mycobacterium tuberculosis dihydrofolate reductase is a target for isoniazid., Argyrou A, Vetting MW, Aladegbami B, Blanchard JS, Nat Struct Mol Biol. 2006 May;13(5):408-13. Epub 2006 Apr 30. PMID:16648861

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