2QD5

Structure of wild type human ferrochelatase in complex with a lead-porphyrin compound

Summary for 2QD5

• Entry DOI: 10.2210/pdb2qd5/pdb
• Related: 2QD1 2QD3 2QD4
• Descriptor: Ferrochelatase, LEAD (II) ION, FE2/S2 (INORGANIC) CLUSTER, ... (9 entities in total)
• Functional Keywords: heme synthesis, ferrochelatase, protoporphyrin ix, lyase
• Biological source: Homo sapiens (human)
• Cellular location: Mitochondrion inner membrane; Peripheral membrane protein; Matrix side: P22830
• Total number of polymer chains: 2
• Total formula weight: 86186.66

Authors

Meldock, A.E.,Dailey, T.A.,Ross, T.A.,Dailey, H.A.,Lanzilotta, W.N. (deposition date: 2007-06-20, release date: 2007-10-30, Last modification date: 2024-02-21)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.3 Å)