2gq2: Difference between revisions
No edit summary |
No edit summary |
||
| Line 4: | Line 4: | ||
|PDB= 2gq2 |SIZE=350|CAPTION= <scene name='initialview01'>2gq2</scene>, resolution 2.10Å | |PDB= 2gq2 |SIZE=350|CAPTION= <scene name='initialview01'>2gq2</scene>, resolution 2.10Å | ||
|SITE= | |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> | |LIGAND= <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=PGE:TRIETHYLENE+GLYCOL'>PGE</scene> | ||
|ACTIVITY= <span class='plainlinks'>[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] </span> | |||
|GENE= thyX, RV2754C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis]) | |GENE= thyX, RV2754C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis]) | ||
|DOMAIN= | |||
|RELATEDENTRY=[[2af6|2AF6]] | |||
|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2gq2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2gq2 OCA], [http://www.ebi.ac.uk/pdbsum/2gq2 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2gq2 RCSB]</span> | |||
}} | }} | ||
| Line 27: | Line 30: | ||
[[Category: Sibley, C H.]] | [[Category: Sibley, C H.]] | ||
[[Category: Turley, S.]] | [[Category: Turley, S.]] | ||
[[Category: bivalent drug]] | [[Category: bivalent drug]] | ||
[[Category: fdt]] | [[Category: fdt]] | ||
| Line 40: | Line 38: | ||
[[Category: tscp]] | [[Category: tscp]] | ||
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 03:19:56 2008'' | ||
Revision as of 00:19, 31 March 2008
| |||||||||||||
| 2gq2, resolution 2.10Å | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Ligands: | GOL, IOD, K, MSE, NAP, PGE | ||||||||||||
| Gene: | thyX, RV2754C (Mycobacterium tuberculosis) | ||||||||||||
| Activity: | Thymidylate synthase (FAD), with EC number 2.1.1.148 | ||||||||||||
| Related: | 2AF6
| ||||||||||||
| Resources: | FirstGlance, OCA, PDBsum, RCSB | ||||||||||||
| 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
Page seeded by OCA on Mon Mar 31 03:19:56 2008
