1QZF

Crystal structure of DHFR-TS from Cryptosporidium hominis

1QZF の概要

• エントリーDOI: 10.2210/pdb1qzf/pdb
• 分子名称: bifunctional dihydrofolate reductase-thymidylate synthase, 2'-DEOXYURIDINE 5'-MONOPHOSPHATE, 10-PROPARGYL-5,8-DIDEAZAFOLIC ACID, ... (6 entities in total)
• 機能のキーワード: bifunctional enzyme, oxidoreductase, transferase
• 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: 311174.94

構造登録者

O'Neil, R.H.,Lilien, R.H.,Donald, B.R.,Stroud, R.M.,Anderson, A.C. (登録日: 2003-09-16, 公開日: 2003-11-11, 最終更新日: 2023-08-23)

主引用文献

O'Neil, R.H.,Lilien, R.H.,Donald, B.R.,Stroud, R.M.,Anderson, A.C.
Phylogenetic classification of protozoa based on the structure of the linker domain in the bifunctional enzyme, dihydrofolate reductase-thymidylate synthase
J.Biol.Chem., 278:52980-52987, 2003

PubMed Abstract: We have determined the crystal structure of dihydrofolate reductase-thymidylate synthase (DHFR-TS) from Cryptosporidium hominis, revealing a unique linker domain containing an 11-residue alpha-helix that has extensive interactions with the opposite DHFR-TS monomer of the homodimeric enzyme. Analysis of the structure of DHFR-TS from C. hominis and of previously solved structures of DHFR-TS from Plasmodium falciparum and Leishmania major reveals that the linker domain primarily controls the relative orientation of the DHFR and TS domains. Using the tertiary structure of the linker domains, we have been able to place a number of protozoa in two distinct and dissimilar structural families corresponding to two evolutionary families and provide the first structural evidence validating the use of DHFR-TS as a tool of phylogenetic classification. Furthermore, the structure of C. hominis DHFR-TS calls into question surface electrostatic channeling as the universal means of dihydrofolate transport between TS and DHFR in the bifunctional enzyme.

PubMed: 14555647
DOI: 10.1074/jbc.M310328200

実験手法

X-RAY DIFFRACTION (2.8 Å)