PDBsum entry 6p4z

Hormone

PDB id: 6p4z

Contents

Protein chains

21 a.a.

30 a.a.

26 a.a.

Metals

_GD

_CO ×2

_CL

Waters ×48

PDB id:

6p4z

Name:

Hormone

Title:

Structure of gadolinium-caged cobalt (iii) insulin hexamer

Structure:

Insulin chain a. Chain: a, c. Engineered: yes. Insulin chain b. Chain: b, d. Engineered: yes

Source:

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

Resolution:

1.80Å R-factor: 0.184 R-free: 0.239

Authors:

T.H.Tran,S.K.Taylor,M.N.Stojanovic,L.Tong

Key ref:

S.K.Taylor et al. (2018). Insulin Hexamer-Caged Gadolinium Ion as MRI Contrast-o-phore. Chemistry, 24, 10646-10652. PubMed id: 29873848 DOI: 10.1002/chem.201801388

Date:

29-May-19 Release date: 12-Jun-19

Protein chains

P01308  (INS_HUMAN) -  Insulin from Homo sapiens

Seq: 110 a.a.

Struc: 21 a.a.

Protein chain

P01308  (INS_HUMAN) -  Insulin from Homo sapiens

Seq: 110 a.a.

Struc: 30 a.a.

Protein chain

P01308  (INS_HUMAN) -  Insulin from Homo sapiens

Seq: 110 a.a.

Struc: 26 a.a.

DOI no: 10.1002/chem.201801388

Chemistry 24:10646-10652 (2018)

PubMed id: 29873848

Insulin Hexamer-Caged Gadolinium Ion as MRI Contrast-o-phore.

S.K.Taylor, T.H.Tran, M.Z.Liu, P.E.Harris, Y.Sun, S.R.Jambawalikar, L.Tong, M.N.Stojanovic.

ABSTRACT

High-relaxivity protein-complexes of Gd^III are being pursued as MRI contrast agents in hope that they can be used at much lower doses that would minimize toxic-side effects of Gd^III release from traditional contrast agents. We construct here a new type of protein-based MRI contrast agent, a proteinaceous cage based on a stable insulin hexamer in which Gd^III is captured inside a water filled cavity. The macromolecular structure and the large number of "free" Gd^III coordination sites available for water binding lead to exceptionally high relaxivities per one Gd^III ion. The Gd^III slowly diffuses out of this cage, but this diffusion can be prevented by addition of ligands that bind to the hexamer. The ligands that trigger structural changes in the hexamer, SCN^- , Cl^- and phenols, modulate relaxivities through an outside-in signaling that is allosterically transduced through the protein cage. Contrast-o-phores based on protein-caged metal ions have potential to become clinical contrast agents with environmentally-sensitive properties.