8PI6

Crystal structure of the monomeric zinc free human insulin A22K, B3E, B26E, B29R, desB30 precursor with a Ser-Glu-Asp-Trp-Trp-Arg C-peptide and a Glu-Glu-Gly-Glu-Pro-Arg N-terminal extension

Summary for 8PI6

• Entry DOI: 10.2210/pdb8pi6/pdb
• Descriptor: Insulin B chain,Insulin A chain (2 entities in total)
• Functional Keywords: insulin, precursor, dimer, hormone
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 36981.35

Authors

Johansson, E.,Schluckebier, G. (deposition date: 2023-06-21, release date: 2023-11-08, Last modification date: 2024-11-13)

Primary citation

Kjeldsen, T.,Andersen, A.S.,Hubalek, F.,Johansson, E.,Kreiner, F.F.,Schluckebier, G.,Kurtzhals, P.
Molecular engineering of insulin for recombinant expression in yeast.
Trends Biotechnol, 42:464-478, 2024

PubMed Abstract: Since the first administration of insulin to a person with diabetes in 1922, scientific contributions from academia and industry have improved insulin therapy and access. The pharmaceutical need for insulin is now more than 40 tons annually, half of which is produced by recombinant secretory expression in Saccharomyces cerevisiae. We discuss how, in this yeast species, adaptation of insulin precursors by removable structural elements is pivotal for efficient secretory expression. The technologies reviewed have been implemented at industrial scale and are seminal for the supply of human insulin and insulin analogues to people with diabetes now and in the future. Engineering of a target protein with removable structural elements may provide a general approach to yield optimisation.

PubMed: 37880066
DOI: 10.1016/j.tibtech.2023.09.012

Experimental method

X-RAY DIFFRACTION (2.14 Å)