2cig: Difference between revisions

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[[Image:2cig.~~gif~~|left|200px]]

[[Image:2cig.png|left|200px]]

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

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

~~==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~~.

The line below this paragraph, {{ABSTRACT_PUBMED_16648861}}, adds the Publication Abstract to the page

(as it appears on PubMed at http://www.pubmed.gov), where 16648861 is the PubMed ID number.

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==About this Structure==

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[[Category: Reductase]]

[[Category: Tuberculosis]]

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on ~~Sat May 3 22~~:13:15 2008''

''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 04:44:17 2008''

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-[[Image:2cig.gif|left|200px]]
+{{Seed}}
+[[Image:2cig.png|left|200px]]
 <!--
@@ Line 9: / Line 10: @@
 {{STRUCTURE_2cig|  PDB=2cig  |  SCENE=  }}
-'''DIHYDROFOLATE REDUCTASE FROM MYCOBACTERIUM TUBERCULOSIS INHIBITED BY THE ACYCLIC 4R ISOMER OF INH-NADP A DERIVATIVE OF THE PRODRUG ISONIAZID.'''
+===DIHYDROFOLATE REDUCTASE FROM MYCOBACTERIUM TUBERCULOSIS INHIBITED BY THE ACYCLIC 4R ISOMER OF INH-NADP A DERIVATIVE OF THE PRODRUG ISONIAZID.===
-==Overview==
+<!--
-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.
+The line below this paragraph, {{ABSTRACT_PUBMED_16648861}}, adds the Publication Abstract to the page
+(as it appears on PubMed at http://www.pubmed.gov), where 16648861 is the PubMed ID number.
+-->
+{{ABSTRACT_PUBMED_16648861}}
 ==About this Structure==
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 [[Category: Reductase]]
 [[Category: Tuberculosis]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May  3 22:13:15 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Jul 28 04:44:17 2008''