6OJS

Crystal structure of TS-DHFR from Cryptosporidium hominis in complex with NADPH, FdUMP, MTX and 2-amino-4-oxo-4,7-dihydro-pyrrolo[2,3-d]pyrimidine-methyl-phenyl-D-glutamic acid

6OJS の概要

• エントリーDOI: 10.2210/pdb6ojs/pdb
• 分子名称: Bifunctional dihydrofolate reductase-thymidylate synthase, NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 5-FLUORO-2'-DEOXYURIDINE-5'-MONOPHOSPHATE, ... (5 entities in total)
• 機能のキーワード: inhibitor, ts, ts-dhfr, transferase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Cryptosporidium hominis
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 311009.68

構造登録者

Czyzyk, D.J.,Anderson, K.S.,Jorgensen, W.L.,Valhondo, M. (登録日: 2019-04-12, 公開日: 2019-06-19, 最終更新日: 2023-10-11)

主引用文献

Czyzyk, D.J.,Valhondo, M.,Jorgensen, W.L.,Anderson, K.S.
Understanding the structural basis of species selective, stereospecific inhibition for Cryptosporidium and human thymidylate synthase.
Febs Lett., 593:2069-2078, 2019

PubMed Abstract: Thymidylate synthase (TS), found in all organisms, is an essential enzyme responsible for the de novo synthesis of deoxythymidine monophosphate. The TS active sites of the protozoal parasite Cryptosporidium hominis and human are relatively conserved. Evaluation of antifolate compound 1 and its R-enantiomer 2 against both enzymes reveals divergent inhibitor selectivity and enzyme stereospecificity. To establish how C. hominis and human TS (ChTS and hTS) selectively discriminate 1 and 2, respectively, we determined crystal structures of ChTS complexed with 2 and hTS complexed with 1 or 2. Coupled with the previously determined structure of ChTS complexed with 1, we discuss a possible mechanism for enzyme stereospecificity and inhibitor selectivity.

PubMed: 31172516
DOI: 10.1002/1873-3468.13474

実験手法

X-RAY DIFFRACTION (3.214 Å)