PDBsum entry 6ctc

Metal transport

PDB id: 6ctc

Contents

Protein chain

673 a.a.

Ligands

CO3

POP

Metals

_FE ×2

Waters ×62

PDB id:

6ctc

Name:

Metal transport

Title:

Crystal structure of human transferrin bound to triferic fpc iron pyrophosphate

Structure:

Serotransferrin. Chain: a. Synonym: transferrin,beta-1 metal-binding globulin,siderophilin. Engineered: yes

Source:

Homo sapiens. Human. Organism_taxid: 9606. Gene: tf, pro1400. Expressed in: homo sapiens. Expression_system_taxid: 9606

Resolution:

2.60Å R-factor: 0.184 R-free: 0.253

Authors:

T.E.Edwards,R.Pratt

Key ref:

R.Pratt et al. (2018). Ferric pyrophosphate citrate: interactions with transferrin. Biometals, 31, 1081-1089. PubMed id: 30311019 DOI: 10.1007/s10534-018-0142-2

Date:

22-Mar-18 Release date: 24-Oct-18

Protein chain

P02787  (TRFE_HUMAN) -  Serotransferrin from Homo sapiens

Seq: 698 a.a.

Struc: 673 a.a.*

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

DOI no: 10.1007/s10534-018-0142-2

Biometals 31:1081-1089 (2018)

PubMed id: 30311019

Ferric pyrophosphate citrate: interactions with transferrin.

R.Pratt, G.J.Handelman, T.E.Edwards, A.Gupta.

ABSTRACT

There are several options available for intravenous application of iron supplements, but they all have a similar structure:-an iron core surrounded by a carbohydrate coating. These nanoparticles require processing by the reticuloendothelial system to release iron, which is subsequently picked up by the iron-binding protein transferrin and distributed throughout the body, with most of the iron supplied to the bone marrow. This process risks exposing cells and tissues to free iron, which is potentially toxic due to its high redox activity. A new parenteral iron formation, ferric pyrophosphate citrate (FPC), has a novel structure that differs from conventional intravenous iron formulations, consisting of an iron atom complexed to one pyrophosphate and two citrate anions. In this study, we show that FPC can directly transfer iron to apo-transferrin. Kinetic analyses reveal that FPC donates iron to apo-transferrin with fast binding kinetics. In addition, the crystal structure of transferrin bound to FPC shows that FPC can donate iron to both iron-binding sites found within the transferrin structure. Examination of the iron-binding sites demonstrates that the iron atoms in both sites are fully encapsulated, forming bonds with amino acid side chains in the protein as well as pyrophosphate and carbonate anions. Taken together, these data demonstrate that, unlike intravenous iron formulations, FPC can directly and rapidly donate iron to transferrin in a manner that does not expose cells and tissues to the damaging effects of free, redox-active iron.