2gq2: Difference between revisions
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'''Mycobacterium tuberculosis ThyX-NADP complex''' | {{Structure | ||
|PDB= 2gq2 |SIZE=350|CAPTION= <scene name='initialview01'>2gq2</scene>, resolution 2.10Å | |||
|SITE= | |||
|LIGAND= <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene> and <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene> | |||
|ACTIVITY= [http://en.wikipedia.org/wiki/Thymidylate_synthase_(FAD) Thymidylate synthase (FAD)], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.1.1.148 2.1.1.148] | |||
|GENE= thyX, RV2754C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis]) | |||
}} | |||
'''Mycobacterium tuberculosis ThyX-NADP complex''' | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
2GQ2 is a [ | 2GQ2 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2GQ2 OCA]. | ||
==Reference== | ==Reference== | ||
NADP+ expels both the co-factor and a substrate analog from the Mycobacterium tuberculosis ThyX active site: opportunities for anti-bacterial drug design., Sampathkumar P, Turley S, Sibley CH, Hol WG, J Mol Biol. 2006 Jun 30;360(1):1-6. Epub 2006 May 12. PMID:[http:// | NADP+ expels both the co-factor and a substrate analog from the Mycobacterium tuberculosis ThyX active site: opportunities for anti-bacterial drug design., Sampathkumar P, Turley S, Sibley CH, Hol WG, J Mol Biol. 2006 Jun 30;360(1):1-6. Epub 2006 May 12. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/16730023 16730023] | ||
[[Category: Mycobacterium tuberculosis]] | [[Category: Mycobacterium tuberculosis]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: NAP]] | [[Category: NAP]] | ||
[[Category: PGE]] | [[Category: PGE]] | ||
[[Category: bivalent | [[Category: bivalent drug]] | ||
[[Category: | [[Category: fdt]] | ||
[[Category: flavin dependent thymidylate synthase]] | [[Category: flavin dependent thymidylate synthase]] | ||
[[Category: inhibitor design]] | [[Category: inhibitor design]] | ||
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[[Category: tscp]] | [[Category: tscp]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 17:07:43 2008'' | ||
Revision as of 15:07, 20 March 2008
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| 2gq2, resolution 2.10Å | |||||||||||||
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| Ligands: | IOD, K, NAP, PGE and GOL | ||||||||||||
| Gene: | thyX, RV2754C (Mycobacterium tuberculosis) | ||||||||||||
| Activity: | Thymidylate synthase (FAD), with EC number 2.1.1.148 | ||||||||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||||||||
Mycobacterium tuberculosis ThyX-NADP complex
Overview
The novel flavin-dependent thymidylate synthase, ThyX, is absent in humans but several pathogenic bacteria depend exclusively on ThyX activity to synthesize thymidylate. Reduction of the enzyme-bound FAD by NADPH is suggested to be the critical first step in ThyX catalysis. We soaked Mycobacterium tuberculosis ThyX-FAD-BrdUMP ternary complex crystals in a solution containing NADP+ to gain structural insights into the reductive step of the catalytic cycle. Surprisingly, the NADP+ displaced both FAD and BrdUMP from the active site. In the resultant ThyX-NADP+ binary complex, the AMP moiety is bound in a deep pocket similar to that of the same moiety of FAD in the ternary complex, while the nicotinamide part of NADP+ is engaged in a limited number of contacts with ThyX. The additional 2'-phosphate group attached to the AMP ribose of NADP+ could be accommodated with minor rearrangement of water molecules. The newly introduced 2'-phosphate groups are engaged in water-mediated interactions across the non-crystallographic 2-fold axis of the ThyX tetramer, suggesting possibilities for design of high-affinity bivalent inhibitors of this intriguing enzyme.
About this Structure
2GQ2 is a Single protein structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.
Reference
NADP+ expels both the co-factor and a substrate analog from the Mycobacterium tuberculosis ThyX active site: opportunities for anti-bacterial drug design., Sampathkumar P, Turley S, Sibley CH, Hol WG, J Mol Biol. 2006 Jun 30;360(1):1-6. Epub 2006 May 12. PMID:16730023
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