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)

2AF6 の概要

• エントリーDOI: 10.2210/pdb2af6/pdb
• 分子名称: Thymidylate synthase thyX, IODIDE ION, FLAVIN-ADENINE DINUCLEOTIDE, ... (6 entities in total)
• 機能のキーワード: m.tuberculosis, thyx, fdts, tscp, flavin dependent thymidylate synthase, transferase
• 由来する生物種: Mycobacterium tuberculosis
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 243699.20

構造登録者

Sampathkumar, P.,Turley, S.,Ulmer, J.E.,Rhie, H.G.,Sibley, C.H.,Hol, W.G. (登録日: 2005-07-25, 公開日: 2005-10-04, 最終更新日: 2024-10-16)

主引用文献

Sampathkumar, P.,Turley, S.,Ulmer, J.E.,Rhie, H.G.,Sibley, C.H.,Hol, W.G.
Structure of the Mycobacterium tuberculosis Flavin Dependent Thymidylate Synthase (MtbThyX) at 2.0A Resolution.
J.Mol.Biol., 352:1091-1104, 2005

PubMed Abstract: 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.

PubMed: 16139296
DOI: 10.1016/j.jmb.2005.07.071

実験手法

X-RAY DIFFRACTION (2.01 Å)