2af6

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[[Image:2af6.gif|left|200px]]
[[Image:2af6.gif|left|200px]]
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{{Structure
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<!--
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|PDB= 2af6 |SIZE=350|CAPTION= <scene name='initialview01'>2af6</scene>, resolution 2.01&Aring;
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The line below this paragraph, containing "STRUCTURE_2af6", creates the "Structure Box" on the page.
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|SITE=
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You may change the PDB parameter (which sets the PDB file loaded into the applet)
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|LIGAND= <scene name='pdbligand=BRU:5-BROMO-2&#39;-DEOXYURIDINE-5&#39;-MONOPHOSPHATE'>BRU</scene>, <scene name='pdbligand=FAD:FLAVIN-ADENINE+DINUCLEOTIDE'>FAD</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=IOD:IODIDE+ION'>IOD</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene>
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or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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|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>
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or leave the SCENE parameter empty for the default display.
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|GENE= thyX ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=1773 Mycobacterium tuberculosis])
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-->
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|DOMAIN=
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{{STRUCTURE_2af6| PDB=2af6 | SCENE= }}
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|RELATEDENTRY=
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2af6 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2af6 OCA], [http://www.ebi.ac.uk/pdbsum/2af6 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2af6 RCSB]</span>
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}}
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'''Crystal structure of Mycobacterium tuberculosis Flavin dependent thymidylate synthase (Mtb ThyX) in the presence of co-factor FAD and substrate analog 5-Bromo-2'-Deoxyuridine-5'-Monophosphate (BrdUMP)'''
'''Crystal structure of Mycobacterium tuberculosis Flavin dependent thymidylate synthase (Mtb ThyX) in the presence of co-factor FAD and substrate analog 5-Bromo-2'-Deoxyuridine-5'-Monophosphate (BrdUMP)'''
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[[Category: Mycobacterium tuberculosis]]
[[Category: Mycobacterium tuberculosis]]
[[Category: Single protein]]
[[Category: Single protein]]
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[[Category: Thymidylate synthase (FAD)]]
 
[[Category: Hol, W G.]]
[[Category: Hol, W G.]]
[[Category: Rhie, H G.]]
[[Category: Rhie, H G.]]
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[[Category: Turley, S.]]
[[Category: Turley, S.]]
[[Category: Ulmer, J E.]]
[[Category: Ulmer, J E.]]
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[[Category: fdt]]
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[[Category: Fdt]]
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[[Category: flavin dependent thymidylate synthase]]
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[[Category: Flavin dependent thymidylate synthase]]
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[[Category: m tuberculosis]]
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[[Category: M tuberculosis]]
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[[Category: thyx]]
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[[Category: Thyx]]
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[[Category: tscp]]
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[[Category: Tscp]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 18:58:27 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Mon Mar 31 01:51:50 2008''
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Revision as of 15:58, 3 May 2008

Template:STRUCTURE 2af6

Crystal structure of Mycobacterium tuberculosis Flavin dependent thymidylate synthase (Mtb ThyX) in the presence of co-factor FAD and substrate analog 5-Bromo-2'-Deoxyuridine-5'-Monophosphate (BrdUMP)


Overview

A novel flavin-dependent thymidylate synthase was identified recently as an essential gene in many archaebacteria and some pathogenic eubacteria. This enzyme, ThyX, is a potential antibacterial drug target, since humans and most eukaryotes lack the thyX gene and depend upon the conventional thymidylate synthase (TS) for their dTMP requirements. We have cloned and overexpressed the thyX gene (Rv2754c) from Mycobacterium tuberculosis in Escherichia coli. The M.tuberculosis ThyX (MtbThyX) enzyme complements the E.coli chi2913 strain that lacks its conventional TS activity. The crystal structure of the homotetrameric MtbThyX was determined in the presence of the cofactor FAD and the substrate analog, 5-bromo-2'-deoxyuridine-5'-monophosphate (BrdUMP). In the active site, which is formed by three monomers, FAD is bound in an extended conformation with the adenosine ring in a deep pocket and BrdUMP in a closed conformation near the isoalloxazine ring. Structure-based mutational studies have revealed a critical role played by residues Lys165 and Arg168 in ThyX activity, possibly by governing access to the carbon atom to be methylated of a totally buried substrate dUMP.

About this Structure

2AF6 is a Single protein structure of sequence from Mycobacterium tuberculosis. Full crystallographic information is available from OCA.

Reference

Structure of the Mycobacterium tuberculosis flavin dependent thymidylate synthase (MtbThyX) at 2.0A resolution., Sampathkumar P, Turley S, Ulmer JE, Rhie HG, Sibley CH, Hol WG, J Mol Biol. 2005 Oct 7;352(5):1091-104. PMID:16139296 Page seeded by OCA on Sat May 3 18:58:27 2008

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