1PV8

Crystal structure of a low activity F12L mutant of human porphobilinogen synthase

1PV8 の概要

• エントリーDOI: 10.2210/pdb1pv8/pdb
• 分子名称: Delta-aminolevulinic acid dehydratase, ZINC ION, 3-(2-AMINOETHYL)-4-(AMINOMETHYL)HEPTANEDIOIC ACID, ... (4 entities in total)
• 機能のキーワード: porphobilinogen synthase, tetrapyrrole biosynthesis, reaction intermediate, lyase
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 72972.77

構造登録者

Breinig, S.,Kervinen, J.,Stith, L.,Wasson, A.S.,Fairman, R.,Wlodawer, A.,Zdanov, A.,Jaffe, E.K. (登録日: 2003-06-26, 公開日: 2003-09-09, 最終更新日: 2024-12-25)

主引用文献

Breinig, S.,Kervinen, J.,Stith, L.,Wasson, A.S.,Fairman, R.,Wlodawer, A.,Zdanov, A.,Jaffe, E.K.
Control of tetrapyrrole biosynthesis by alternate quaternary forms of porphobilinogen synthase.
Nat.Struct.Biol., 10:757-763, 2003

PubMed Abstract: Porphobilinogen synthase (PBGS) catalyzes the first common step in the biosynthesis of tetrapyrroles (such as heme and chlorophyll). Although the predominant oligomeric form of this enzyme, as inferred from many crystal structures, is that of a homo-octamer, a rare human PBGS allele, F12L, reveals the presence of a hexameric form. Rearrangement of an N-terminal arm is responsible for this oligomeric switch, which results in profound changes in kinetic behavior. The structural transition between octamer and hexamer must proceed through an unparalleled equilibrium containing two different dimer structures. The allosteric magnesium, present in most PBGS, has a binding site in the octamer but not in the hexamer. The unprecedented structural rearrangement reported here relates to the allosteric regulation of PBGS and suggests that alternative PBGS oligomers may function in a magnesium-dependent regulation of tetrapyrrole biosynthesis in plants and some bacteria.

PubMed: 12897770
DOI: 10.1038/nsb963

実験手法

X-RAY DIFFRACTION (2.2 Å)