2af6
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(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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Revision as of 05:58, 21 November 2007
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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 IOD, FAD and GOL 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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