3E4A

Human IDE-inhibitor complex at 2.6 angstrom resolution

Summary for 3E4A

• Entry DOI: 10.2210/pdb3e4a/pdb
• Descriptor: Insulin-degrading enzyme, HYDROXAMATE PEPTIDE II1, ZINC ION, ... (7 entities in total)
• Functional Keywords: insulin, hydroxamate, insulin degrading enzyme, hydrolase, metal-binding, metalloprotease, protease
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: P14735
• Total number of polymer chains: 4
• Total formula weight: 239073.28

Authors

Malito, E.,Leissring, M.A.,Choi, S.,Cuny, G.D.,Tang, W.J. (deposition date: 2008-08-11, release date: 2009-05-19, Last modification date: 2023-08-30)

Primary citation

Leissring, M.A.,Malito, E.,Hedouin, S.,Reinstatler, L.,Sahara, T.,Abdul-Hay, S.O.,Choudhry, S.,Maharvi, G.M.,Fauq, A.H.,Huzarska, M.,May, P.S.,Choi, S.,Logan, T.P.,Turk, B.E.,Cantley, L.C.,Manolopoulou, M.,Tang, W.J.,Stein, R.L.,Cuny, G.D.,Selkoe, D.J.
Designed inhibitors of insulin-degrading enzyme regulate the catabolism and activity of insulin.
Plos One, 5:e10504-e10504, 2010

PubMed Abstract: Insulin is a vital peptide hormone that is a central regulator of glucose homeostasis, and impairments in insulin signaling cause diabetes mellitus. In principle, it should be possible to enhance the activity of insulin by inhibiting its catabolism, which is mediated primarily by insulin-degrading enzyme (IDE), a structurally and evolutionarily distinctive zinc-metalloprotease. Despite interest in pharmacological inhibition of IDE as an attractive anti-diabetic approach dating to the 1950s, potent and selective inhibitors of IDE have not yet emerged.

PubMed: 20498699
DOI: 10.1371/journal.pone.0010504

Experimental method

X-RAY DIFFRACTION (2.6 Å)