2QD3

Wild type human ferrochelatase crystallized with ammonium sulfate

2QD3 の概要

• エントリーDOI: 10.2210/pdb2qd3/pdb
• 関連するPDBエントリー: 2QD1 2QD4 2QD5
• 分子名称: Ferrochelatase, FE2/S2 (INORGANIC) CLUSTER, CHOLIC ACID, ... (6 entities in total)
• 機能のキーワード: heme synthesis, ferrochelatase, protoporphyrin ix, lyase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Mitochondrion inner membrane; Peripheral membrane protein; Matrix side: P22830
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 85459.85

構造登録者

Medlock, A.E.,Dailey, T.A.,Ross, T.A.,Dailey, H.A.,Lanzilotta, W.N. (登録日: 2007-06-20, 公開日: 2007-10-30, 最終更新日: 2024-02-21)

主引用文献

Medlock, A.E.,Dailey, T.A.,Ross, T.A.,Dailey, H.A.,Lanzilotta, W.N.
A pi-Helix Switch Selective for Porphyrin Deprotonation and Product Release in Human Ferrochelatase.
J.Mol.Biol., 373:1006-1016, 2007

PubMed Abstract: Ferrochelatase (protoheme ferrolyase, EC 4.99.1.1) is the terminal enzyme in heme biosynthesis and catalyzes the insertion of ferrous iron into protoporphyrin IX to form protoheme IX (heme). Due to the many critical roles of heme, synthesis of heme is required by the vast majority of organisms. Despite significant investigation of both the microbial and eukaryotic enzyme, details of metal chelation remain unidentified. Here we present the first structure of the wild-type human enzyme, a lead-inhibited intermediate of the wild-type enzyme with bound metallated porphyrin macrocycle, the product bound form of the enzyme, and a higher resolution model for the substrate-bound form of the E343K variant. These data paint a picture of an enzyme that undergoes significant changes in secondary structure during the catalytic cycle. The role that these structural alterations play in overall catalysis and potential protein-protein interactions with other proteins, as well as the possible molecular basis for these changes, is discussed. The atomic details and structural rearrangements presented herein significantly advance our understanding of the substrate binding mode of ferrochelatase and reveal new conformational changes in a structurally conserved pi-helix that is predicted to have a central role in product release.

PubMed: 17884090
DOI: 10.1016/j.jmb.2007.08.040

実験手法

X-RAY DIFFRACTION (2.2 Å)