2af6
From Proteopedia
(New page: 200px<br /><applet load="2af6" size="450" color="white" frame="true" align="right" spinBox="true" caption="2af6, resolution 2.01Å" /> '''Crystal structure of...) |
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| - | [[Image:2af6.gif|left|200px]]<br /><applet load="2af6" size=" | + | [[Image:2af6.gif|left|200px]]<br /><applet load="2af6" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="2af6, resolution 2.01Å" /> | caption="2af6, resolution 2.01Å" /> | ||
'''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)'''<br /> | '''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)'''<br /> | ||
==Overview== | ==Overview== | ||
| - | A novel flavin-dependent thymidylate synthase was identified recently as | + | 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== | ==About this Structure== | ||
| - | 2AF6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with IOD, FAD and GOL as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http:// | + | 2AF6 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mycobacterium_tuberculosis Mycobacterium tuberculosis] with <scene name='pdbligand=IOD:'>IOD</scene>, <scene name='pdbligand=FAD:'>FAD</scene> and <scene name='pdbligand=GOL:'>GOL</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AF6 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Thymidylate synthase (FAD)]] | [[Category: Thymidylate synthase (FAD)]] | ||
| - | [[Category: Hol, W | + | [[Category: Hol, W G.]] |
| - | [[Category: Rhie, H | + | [[Category: Rhie, H G.]] |
[[Category: Sampathkumar, P.]] | [[Category: Sampathkumar, P.]] | ||
| - | [[Category: Sibley, C | + | [[Category: Sibley, C H.]] |
[[Category: Turley, S.]] | [[Category: Turley, S.]] | ||
| - | [[Category: Ulmer, J | + | [[Category: Ulmer, J E.]] |
[[Category: FAD]] | [[Category: FAD]] | ||
[[Category: GOL]] | [[Category: GOL]] | ||
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[[Category: fdts]] | [[Category: fdts]] | ||
[[Category: flavin dependent thymidylate synthase]] | [[Category: flavin dependent thymidylate synthase]] | ||
| - | [[Category: m | + | [[Category: m tuberculosis]] |
[[Category: thyx]] | [[Category: thyx]] | ||
[[Category: tscp]] | [[Category: tscp]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:26:47 2008'' |
Revision as of 14:26, 21 February 2008
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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)
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 with , and as ligands. Active as Thymidylate synthase (FAD), with EC number 2.1.1.148 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
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