4LTE: Cysteine-free Human Insulin Degrading Enzyme

Structure of Cysteine-free Human Insulin Degrading Enzyme in Complex with Macrocyclic Inhibitor. Determined by X-ray diffraction at 2.71 Å resolution. Released 21 May 2014.

Method
X-ray diffraction
Resolution
2.71 Å
Organisms
Homo sapiens, synthetic construct
Chains
4
Atoms
16,216
Mol. weight
228.6 kDa
Ligands
FUM, LYN, ZN
Released
21 May 2014

Explore 4LTE in 3D Show helices and sheets RCSB PDB PDBe

Secondary structure: helices and β-sheets

4LTE contains 119 α-helices and 68 β-strands across 2 chains. Residue ranges use author residue numbering, as in the PDB file, from PDBe. To see them in 3D, choose the Cartoon representation with Secondary structure coloring: helices, sheets and coils get different colors.

Chain A: 60 helices, 34 β-strands

ElementResiduesLengthSheet
β-strand47-5041
β-strand63-6971
β-strand74-7961
β-strand85-9281
α-helix96-983
α-helix106-1138
α-helix114-1163
β-strand11812
α-helix126-1327
β-strand137-14261
β-strand147-15481
α-helix155-1573
α-helix158-1669
α-helix167-1693
β-strand17212
α-helix176-19419
α-helix197-20711
α-helix214-2163
α-helix2231
α-helix224-2285
α-helix229-2324
α-helix237-24812
α-helix251-2533
β-strand254-26071
α-helix264-27512
α-helix283-2864
α-helix295-2973
β-strand300-30453
β-strand312-31983
α-helix323-3253
α-helix330-3389
α-helix346-3527
β-strand359-36793
β-strand370-37893
α-helix381-3844
α-helix387-40418
α-helix408-42316
α-helix425-4295
α-helix430-44011
α-helix446-4483
α-helix461-4688
α-helix473-4753
β-strand477-48153
α-helix483-4853
β-strand491-49223
β-strand499-50463
α-helix505-5062
α-helix507-5148
α-helix524-5274
α-helix538-5414
β-strand549-55354
β-strand557-56374
β-strand571-57994
α-helix581-5833
α-helix587-61327
β-strand616-62274
β-strand626-63494
α-helix638-65013
α-helix656-67116
α-helix672-6754
α-helix678-69013
β-strand69115
α-helix697-7048
α-helix709-72113
β-strand722-72326
β-strand724-73184
α-helix735-75319
β-strand756-75726
α-helix758-7592
α-helix760-7623
α-helix764-7674
β-strand76815
β-strand76917
α-helix771-7722
β-strand775-78288
β-strand789-799118
α-helix802-82019
α-helix821-8266
β-strand833-84088
β-strand843-852108
α-helix856-87621
α-helix879-89416
α-helix895-8973
α-helix900-91213
α-helix920-92910
α-helix933-9397
α-helix940-9445
β-strand952-95988
α-helix981-9899
β-strand990-99128
α-helix9921
α-helix995-10006
β-strand100417
α-helix1005-10106
Chain B: 59 helices, 34 β-strands
ElementResiduesLengthSheet
β-strand47-5159
β-strand63-6979
β-strand74-7969
β-strand85-9289
α-helix96-983
α-helix106-1138
β-strand118110
α-helix126-1338
β-strand137-14269
β-strand147-15489
α-helix155-1573
α-helix158-1669
α-helix167-1693
β-strand172110
α-helix176-19419
α-helix197-20711
α-helix214-2163
α-helix2231
α-helix224-2285
α-helix229-2324
α-helix237-24812
α-helix251-2533
β-strand254-26079
α-helix264-27512
α-helix283-2864
α-helix295-2973
β-strand300-304511
β-strand312-319811
α-helix323-3253
α-helix330-3389
α-helix346-3527
β-strand359-367911
β-strand370-378911
α-helix381-3844
α-helix387-40418
α-helix408-42316
α-helix425-4295
α-helix430-44011
α-helix446-4483
α-helix461-4688
α-helix473-4753
β-strand477-481511
α-helix483-4853
β-strand491-492211
β-strand499-504611
α-helix505-5062
α-helix507-5148
α-helix524-5274
α-helix538-5414
β-strand549-553512
β-strand557-563712
β-strand571-579912
α-helix587-61327
β-strand616-622712
β-strand626-634912
α-helix638-65013
α-helix656-67116
α-helix672-6754
α-helix678-69013
β-strand691113
α-helix697-7048
α-helix709-72113
β-strand722-723214
β-strand724-731812
α-helix735-75319
β-strand756-757214
α-helix758-7592
α-helix760-7623
α-helix764-7674
β-strand768113
β-strand76917
α-helix771-7722
β-strand775-782815
β-strand789-7991115
α-helix802-82019
α-helix821-8266
β-strand832-840915
β-strand843-8521015
α-helix856-87621
α-helix879-89416
α-helix895-8973
α-helix900-91213
α-helix920-9289
α-helix933-9397
α-helix940-9445
β-strand952-959815
α-helix981-9855
α-helix987-9893
β-strand990-991215
α-helix9921
α-helix995-10006
β-strand100417
α-helix1005-10106

Molecules and chains

MoleculeChainsTypeLengthOrganismUniProt
Insulin-degrading enzymeA, Bprotein978Homo sapiensP14735 (AlphaFold model)
Macrocyclic InhibitorM, Nprotein3synthetic construct
Sequence of entity 1 (A, B), FASTA
>4LTE_1 Insulin-degrading enzyme (chains A, B)
MNNPAIKRIGNHITKSPEDKREYRGLELANGIKVLLISDPTTDKSSAALDVHIGSLSDPP
NIAGLSHFLQHMLFLGTKKYPKENEYSQFLSEHAGSSNAFTSGEHTNYYFDVSHEHLEGA
LDRFAQFFLSPLFDESAKDREVNAVDSEHEKNVMNDAWRLFQLEKATGNPKHPFSKFGTG
NKYTLETRPNQEGIDVRQELLKFHSAYYSSNLMAVVVLGRESLDDLTNLVVKLFSEVENK
NVPLPEFPEHPFQEEHLKQLYKIVPIKDIRNLYVTFPIPDLQKYYKSNPGHYLGHLIGHE
GPGSLLSELKSKGWVNTLVGGQKEGARGFMFFIINVDLTEEGLLHVEDIILHMFQYIQKL
RAEGPQEWVFQELKDLNAVAFRFKDKERPRGYTSKIAGILHYYPLEEVLTAEYLLEEFRP
DLIEMVLDKLRPENVRVAIVSKSFEGKTDRTEEWYGTQYKQEAIPDEVIKKWQNADLNGK
FKLPTKNEFIPTNFEILPLEKEATPYPALIKDTAMSKLWFKQDDKFFLPKANLNFEFFSP
FAYVDPLHSNMAYLYLELLKDSLNEYAYAAELAGLSYDLQNTIYGMYLSVKGYNDKQPIL
LKKIIEKMATFEIDEKRFEIIKEAYMRSLNNFRAEQPHQHAMYYLRLLMTEVAWTKDELK
EALDDVTLPRLKAFIPQLLSRLHIEALLHGNITKQAALGIMQMVEDTLIEHAHTKPLLPS
QLVRYREVQLPDRGWFVYQQRNEVHNNSGIEIYYQTDMQSTSENMFLELFAQIISEPAFN
TLRTKEQLGYIVFSGPRRANGIQGLRFIIQSEKPPHYLESRVEAFLITMEKSIEDMTEEA
FQKHIQALAIRRLDKPKKLSAESAKYWGEIISQQYNFDRDNTEVAYLKTLTKEDIIKFYK
EMLAVDAPRRHKVSVHVLAREMDSNPVVGEFPAQNDINLSQAPALPQPEVIQNMTEFKRG
LPLFPLVKPHINFMAAKL
Sequence of entity 2 (M, N), FASTA
>4LTE_2 Macrocyclic Inhibitor (chains M, N)
QFX

Ligands and cofactors

IDNameFormulaCopies
FUMFumaric acidC4 H4 O42
LYN2,6-diamino-hexanoic acid amideC6 H16 N3 O2
ZNZinc ionZn2

Water and common crystallization additives (EPE) are not listed.

Primary citation

Anti-diabetic activity of insulin-degrading enzyme inhibitors mediated by multiple hormones. Maianti, J.P., McFedries, A., Foda, Z.H. et al. Nature (2014) 511:94-98. DOI 10.1038/nature13297 · PubMed

Other PDB entries of the same protein (UniProt P14735 (AlphaFold model), which also has an AlphaFold model), best resolution first:

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