4KAR

Crystal structure of FDTS (TM0449) mutant (H53D) with FAD

4KAR の概要

• エントリーDOI: 10.2210/pdb4kar/pdb
• 関連するPDBエントリー: 4KAS 4KAT
• 分子名称: Thymidylate synthase, FLAVIN-ADENINE DINUCLEOTIDE, NONAETHYLENE GLYCOL, ... (4 entities in total)
• 機能のキーワード: thyx, fdts, h53d mutant, fad, novel fdts fold, convertion of dump to dtmp using tetrahydrofolate, and nad(p)h, transferase
• 由来する生物種: Thermotoga maritima MSB8
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 113479.17

構造登録者

Mathews, I.I. (登録日: 2013-04-22, 公開日: 2014-03-26, 最終更新日: 2023-09-20)

主引用文献

Mathews, I.I.
Flavin-Dependent Thymidylate Synthase as a Drug Target for Deadly Microbes: Mutational Study and a Strategy for Inhibitor Design.
J Bioterror Biodef, Suppl 12:004-004, 2013

PubMed Abstract: The identification of flavin-dependent thymidylate synthase (FDTS) as an essential enzyme and its occurrence in several pathogenic microbes opens opportunities for using FDTS enzyme as an excellent target for new antimicrobial drug discovery. In contrast to the human thymidylate synthase enzyme that utilizes methylene-tetrahydrofolate (CHH folate) for the conversion of dUMP to dTMP, the microbial enzymes utilize an additional non-covalently bound FAD molecule for the hydride transfer from NAD(P)H. The structural and mechanistic differences between the human and microbial enzymes present an attractive opportunity for the design of antimicrobial compounds specific for the pathogens. We have determined the crystal structure of FDTS enzyme in complex with the methyl donor, CHH folate. We describe here the structure of a FDTS mutant and compare it with other FDTS complex structures, including a FDTS-CHH folate complex. We identified a conformational change essential for substrate binding and propose a strategy for the design of FDTS specific inhibitors.

PubMed: 24563811
DOI: 10.4172/2157-2526.S12-004

実験手法

X-RAY DIFFRACTION (2.03 Å)