Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Ensemble cryoEM elucidates the mechanism of insulin capture and degradation by human insulin degrading enzyme.
Journal, issue, pages	Elife, Vol. 7, Year 2018
Publish date	Mar 29, 2018
Authors	Zhening Zhang / Wenguang G Liang / Lucas J Bailey / Yong Zi Tan / Hui Wei / Andrew Wang / Mara Farcasanu / Virgil A Woods / Lauren A McCord / David Lee / Weifeng Shang / Rebecca Deprez-Poulain / Benoit Deprez / David R Liu / Akiko Koide / Shohei Koide / Anthony A Kossiakoff / Sheng Li / Bridget Carragher / Clinton S Potter / Wei-Jen Tang /
PubMed Abstract	Insulin degrading enzyme (IDE) plays key roles in degrading peptides vital in type two diabetes, Alzheimer's, inflammation, and other human diseases. However, the process through which IDE recognizes ...Insulin degrading enzyme (IDE) plays key roles in degrading peptides vital in type two diabetes, Alzheimer's, inflammation, and other human diseases. However, the process through which IDE recognizes peptides that tend to form amyloid fibrils remained unsolved. We used cryoEM to understand both the apo- and insulin-bound dimeric IDE states, revealing that IDE displays a large opening between the homologous ~55 kDa N- and C-terminal halves to allow selective substrate capture based on size and charge complementarity. We also used cryoEM, X-ray crystallography, SAXS, and HDX-MS to elucidate the molecular basis of how amyloidogenic peptides stabilize the disordered IDE catalytic cleft, thereby inducing selective degradation by substrate-assisted catalysis. Furthermore, our insulin-bound IDE structures explain how IDE processively degrades insulin by stochastically cutting either chain without breaking disulfide bonds. Together, our studies provide a mechanism for how IDE selectively degrades amyloidogenic peptides and offers structural insights for developing IDE-based therapies.
External links	Elife / PubMed:29596046 / PubMed Central
Methods	EM (single particle) / X-ray diffraction
Resolution	3.7 - 7.2 Å
Structure data	7041 6b3q 6bfc EMDB-7041, PDB-6b3q, PDB-6bfc: Cryo-EM structure of human insulin degrading enzyme in complex with insulin Method: EM (single particle) / Resolution: 3.7 Å 7062 6b70 EMDB-7062: Cryo-EM structure of human insulin degrading enzyme in complex with insulin PDB-6b70: Cryo-EM structure of human insulin degrading enzyme in complex with FAB H11-E heavy chain, FAB H11-E light chain and insulin Method: EM (single particle) / Resolution: 3.7 Å 7065 6b7y EMDB-7065: Cryo-EM structure of human insulin degrading enzyme in complex with insulin PDB-6b7y: Cryo-EM structure of human insulin degrading enzyme Method: EM (single particle) / Resolution: 6.5 Å 7066 6b7z EMDB-7066: Cryo-EM structure of human insulin degrading enzyme in complex with insulin PDB-6b7z: Cryo-EM structure of human insulin degrading enzyme in complex with FAB H11 heavy chain and FAB H11 light chain Method: EM (single particle) / Resolution: 6.5 Å 7090 6bf6 EMDB-7090, PDB-6bf6: Cryo-EM structure of human insulin degrading enzyme Method: EM (single particle) / Resolution: 6.5 Å 7091 6bf7 EMDB-7091, PDB-6bf7: Cryo-EM structure of human insulin degrading enzyme in complex with FAB H11-E heavy chain, FAB H11-E light chain Method: EM (single particle) / Resolution: 6.5 Å 7092 6bf8 EMDB-7092, PDB-6bf8: Cryo-EM structure of human insulin degrading enzyme in complex with insulin Method: EM (single particle) / Resolution: 4.2 Å 7093 6bf9 EMDB-7093, PDB-6bf9: Cryo-EM structure of human insulin degrading enzyme in complex with FAB H11-E heavy chain, FAB H11-E light chain Method: EM (single particle) / Resolution: 7.2 Å PDB-5wob: Crystal Structure Analysis of Fab1-Bound Human Insulin Degrading Enzyme (IDE) in Complex with Insulin Method: X-RAY DIFFRACTION / Resolution: 3.95 Å
Chemicals	ChemComp-ZN: Unknown entry
Source	homo sapiens (human) mus musculoides (Temminck's mouse) mus musculus (house mouse)
Keywords	HYDROLASE / complex / HYDROLASE/HORMONE / IDE / insulin degrading enzyme / amyloid beta / HYDROLASE-HORMONE complex / HYDROLASE/IMMUNE SYSTEM/HORMONE / BIOSYNTHETIC PROTEIN / HYDROLASE-IMMUNE SYSTEM-HORMONE complex / HYDROLASE/IMMUNE SYSTEM / HYDROLASE-IMMUNE SYSTEM complex / HORMONE