PDBsum entry 2qd2

Biosynthetic protein

PDB id: 2qd2

Contents

Protein chain

359 a.a. *

Ligands

BCT ×2

FES ×2

IMD ×3

CHD ×4

HEM ×2

Waters ×385

* Residue conservation analysis

PDB id:

2qd2

Name:

Biosynthetic protein

Title:

F110a variant of human ferrochelatase with protoheme bound

Structure:

Ferrochelatase. Chain: a, b. Engineered: yes. Mutation: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: dkfzp686p18130. Expressed in: escherichia coli. Expression_system_taxid: 562

Resolution:

2.20Å R-factor: 0.220 R-free: 0.261

Authors:

A.E.Medlock,T.A.Dailey,T.A.Ross,H.A.Dailey,W.N.Lanzilota

Key ref:

A.E.Medlock et al. (2007). A pi-helix switch selective for porphyrin deprotonation and product release in human ferrochelatase. J Mol Biol, 373, 1006-1016. PubMed id: 17884090 DOI: 10.1016/j.jmb.2007.08.040

Date:

20-Jun-07 Release date: 30-Oct-07

Protein chains

P22830  (HEMH_HUMAN) -  Ferrochelatase, mitochondrial from Homo sapiens

Seq: 423 a.a.

Struc: 359 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.4.98.1.1 - protoporphyrin ferrochelatase.
• Reaction: heme b + 2 H⁺ = protoporphyrin IX + Fe²⁺

heme b + 2 × H(+) = protoporphyrin IX + Fe(2+) (Bound ligand (Het Group name = HEM) matches with 97.67% similarity)

Molecule diagrams generated from .mol files obtained from the KEGG ftp site

Added reference

DOI no: 10.1016/j.jmb.2007.08.040

J Mol Biol 373:1006-1016 (2007)

PubMed id: 17884090

A pi-helix switch selective for porphyrin deprotonation and product release in human ferrochelatase.

A.E.Medlock, T.A.Dailey, T.A.Ross, H.A.Dailey, W.N.Lanzilotta.

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.

Selected figure(s)

Figure 1.
Figure 1. Occupancy of the active site for WT1 and R115L. (a) Overlay of cholate residues and the side-chains of H263, R115 and M76 of the WT1 model with the model previously reported for the R115L variant of human ferrochelatase. (b) Heme molecule modeled into the density present in the active site of monomer B of the WT1 data with side-chains of M76 below and H263 above the macrocycle ring. All atoms in the WT1 model are represented as sticks with nitrogen, oxygen, carbon, sulfur, and iron atoms colored blue, red, tan, cyan, and black, respectively. All atoms in the model previously reported for R115L variant are colored green in (a). In all cases the 2F[o]–F[c] composite omit map was generated using the simulated annealing protocol and is contoured at 1 σ (purple and green cage in (a) and (b), respectively).

Figure 5.
Figure 5. Electrostatic surface potential showing the active site region for the (a) wild-type, (b) the substrate bound, and (c) heme bound human ferrochelatase. For clarity, the upper lip and π-helix regions are highlighted. The Figure was generated with PyMOL [http://pymol.sourceforge.net/].

The above figures are reprinted from an Open Access publication published by Elsevier: J Mol Biol (2007, 373, 1006-1016) copyright 2007.

Figures were selected by an automated process.