4EWX

Human Insulin

Summary for 4EWX

• Entry DOI: 10.2210/pdb4ewx/pdb
• Related: 4EWW 4EWZ 4EX0 4EX1
• Descriptor: Insulin A chain, Insulin B chain, ZINC ION, ... (5 entities in total)
• Functional Keywords: hormone
• Biological source: Homo sapiens (human); More
• Cellular location: Secreted: P01308 P01308
• Total number of polymer chains: 4
• Total formula weight: 11837.03

Authors

Favero-Retto, M.P.,Palmieri, L.C.,Lima, L.M.T.R. (deposition date: 2012-04-28, release date: 2013-05-01, Last modification date: 2017-11-15)

Primary citation

Favero-Retto, M.P.,Palmieri, L.C.,Souza, T.A.,Almeida, F.C.,Lima, L.M.
Structural meta-analysis of regular human insulin in pharmaceutical formulations.
Eur J Pharm Biopharm, 85:1112-1121, 2013

PubMed Abstract: We have studied regular acting, wild-type human insulin at potency of 100 U/mL from four different pharmaceutical products directly from their final finished formulation by the combined use of mass spectrometry (MS), dynamic light scattering (DLS), small-angle X-ray scattering (SAXS), nuclear magnetic resonance (NMR), and single-crystal protein crystallography (PX). All products showed similar oligomeric assembly in solution as judged by DLS and SAXS measurements. The NMR spectra were compatible with well folded proteins, showing close conformational identity for the human insulin in the four products. Crystallographic assays conducted with the final formulated products resulted in all insulin crystals belonging to the R3 space group with two a dimer in the asymmetric unit, both with the B-chain in the T configuration. Meta-analysis of the 24 crystal structures solved from the four distinct insulin products revealed close similarity between them regardless of variables such as biological origin, product batch, country origin of the product, and analytical approach, revealing a low conformational variability for the converging insulin structural ensemble. We propose the use of MS, SAXS, NMR fingerprint, and PX as a precise chemical and structural proof of folding identity of regular insulin in the final, formulated product.

PubMed: 23692694
DOI: 10.1016/j.ejpb.2013.05.005

Experimental method

X-RAY DIFFRACTION (2.201 Å)