2CG8

The bifunctional dihydroneopterin aldolase 6-hydroxymethyl-7,8- dihydropterin synthase from Streptococcus pneumoniae

2CG8 の概要

• エントリーDOI: 10.2210/pdb2cg8/pdb
• 分子名称: DIHYDRONEOPTERIN ALDOLASE 6-HYDROXYMETHYL-7,8-DIHYDROPTERIN SYNTHASE (1 entity in total)
• 機能のキーワード: lyase/transferase, aldolase, folate biosynthesis, pyrophosphokinase, lyase, multifunctional enzyme, transferase, lyase-transferase complex
• 由来する生物種: STREPTOCOCCUS PNEUMONIAE
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 124530.93

構造登録者

Garcon, A.,Levy, C.,Derrick, J.P. (登録日: 2006-02-28, 公開日: 2006-06-21, 最終更新日: 2023-12-13)

主引用文献

Garcon, A.,Levy, C.,Derrick, J.P.
Crystal Structure of the Bifunctional Dihydroneopterin Aldolase/6-Hydroxymethyl-7,8-Dihydropterin Pyrophosphokinase from Streptococcus Pneumoniae.
J.Mol.Biol., 360:644-, 2006

PubMed Abstract: The enzymes dihydroneopterin aldolase (DHNA) and 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) catalyse two consecutive steps in the biosynthesis of folic acid. Neither of these enzymes has a counterpart in mammals, and they have therefore been suggested as ideal targets for antimicrobial drugs. Some of the enzymes within the folate pathway can occur as bi- or trifunctional complexes in bacteria and parasites, but the way in which bifunctional DHNA-HPPK enzymes are assembled is unclear. Here, we report the determination of the structure at 2.9 A resolution of the DHNA-HPPK (SulD) bifunctional enzyme complex from the respiratory pathogen Streptococcus pneumoniae. In the crystal, DHNA is assembled as a core octamer, with 422 point group symmetry, although the enzyme is active as a tetramer in solution. Individual HPPK monomers are arranged at the ends of the DHNA octamer, making relatively few contacts with the DHNA domain, but more extensive interactions with adjacent HPPK domains. As a result, the structure forms an elongated cylinder, with the HPPK domains forming two tetramers at each end. The active sites of both enzymes face outward, and there is no clear channel between them that could be used for channelling substrates. The HPPK-HPPK interface accounts for about one-third of the total area between adjacent monomers in SulD, and has levels of surface complementarity comparable to that of the DHNA-DHNA interfaces. There is no "linker" polypeptide between DHNA and HPPK, reducing the conformational flexibility of the HPPK domain relative to the DHNA domain. The implications for the organisation of bi- and trifunctional enzyme complexes within the folate biosynthesis pathway are discussed.

PubMed: 16781731
DOI: 10.1016/J.JMB.2006.05.038

実験手法

X-RAY DIFFRACTION (2.9 Å)