4PFC: Insulin degrading enzyme

Crystal structure of insulin degrading enzyme complexed with inhibitor. Determined by X-ray diffraction at 2.21 Å resolution. Released 17 Jun 2015.

Method
X-ray diffraction
Resolution
2.21 Å
Organism
Homo sapiens
Chains
2
Atoms
16,390
Mol. weight
230.59 kDa
Ligands
2QX, ZN
Released
17 Jun 2015

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

Secondary structure: helices and β-sheets

4PFC contains 112 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: 54 helices, 34 β-strands

ElementResiduesLengthSheet
β-strand47-5041
β-strand63-6971
β-strand74-7961
β-strand85-9281
α-helix96-983
α-helix106-1149
β-strand11812
α-helix126-1338
β-strand137-14261
β-strand147-15481
α-helix155-1573
α-helix158-1669
α-helix167-1693
β-strand17212
α-helix176-1783
α-helix179-19416
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-strand312-32093
α-helix323-3253
α-helix330-3389
α-helix346-3527
β-strand359-36793
β-strand370-37893
α-helix383-3853
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-strand491-49333
β-strand498-50473
α-helix505-5062
α-helix507-5148
α-helix538-5414
β-strand549-55354
β-strand557-56374
β-strand571-57994
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-helix766-7672
β-strand76815
β-strand76917
α-helix771-7722
β-strand775-78288
β-strand789-799118
α-helix802-81918
α-helix820-8267
β-strand830-840118
β-strand843-852108
α-helix856-87621
α-helix879-89416
α-helix900-91213
α-helix920-93011
α-helix933-94311
β-strand952-95988
β-strand990-99128
α-helix995-10006
β-strand100417
α-helix1008-10103
Chain B: 58 helices, 34 β-strands
ElementResiduesLengthSheet
β-strand47-5049
β-strand63-6979
β-strand74-7969
β-strand85-9289
α-helix96-983
α-helix106-1149
β-strand118110
α-helix125-1339
β-strand137-14269
β-strand147-15489
α-helix155-1573
α-helix158-16710
β-strand172110
α-helix176-1783
α-helix179-19315
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-helix279-2802
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-helix383-3853
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-helix536-5416
β-strand549-553512
β-strand557-563712
β-strand571-579912
α-helix587-61327
β-strand616-622712
β-strand626-634912
α-helix638-65114
α-helix656-67116
α-helix672-6754
α-helix678-69013
β-strand691113
α-helix697-7048
α-helix709-72012
β-strand722-723214
β-strand724-731812
α-helix735-75319
β-strand756-757214
α-helix758-7592
α-helix760-7623
α-helix766-7672
β-strand768113
β-strand76917
α-helix771-7722
β-strand775-782815
β-strand789-7991115
α-helix802-81918
α-helix820-8267
β-strand832-840915
β-strand843-8521015
α-helix856-87621
α-helix879-89315
α-helix895-8973
α-helix900-91213
α-helix920-9289
α-helix933-9397
α-helix940-9445
β-strand952-959815
α-helix981-9844
α-helix986-9894
β-strand990-991215
α-helix995-10006
β-strand100417
α-helix1007-10115

Molecules and chains

MoleculeChainsTypeLengthOrganismUniProt
Insulin-degrading enzymeA, Bprotein989Homo sapiensP14735 (AlphaFold model)
Sequence of entity 1 (A, B), FASTA
>4PFC_1 Insulin-degrading enzyme (chains A, B)
MGHHHHHHGRAMNNPAIKRIGNHITKSPEDKREYRGLELANGIKVLLISDPTTDKSSAAL
DVHIGSLSDPPNIAGLSHFLQHMLFLGTKKYPKENEYSQFLSEHAGSSNAFTSGEHTNYY
FDVSHEHLEGALDRFAQFFLSPLFDESAKDREVNAVDSEHEKNVMNDAWRLFQLEKATGN
PKHPFSKFGTGNKYTLETRPNQEGIDVRQELLKFHSAYYSSNLMAVVVLGRESLDDLTNL
VVKLFSEVENKNVPLPEFPEHPFQEEHLKQLYKIVPIKDIRNLYVTFPIPDLQKYYKSNP
GHYLGHLIGHEGPGSLLSELKSKGWVNTLVGGQKEGARGFMFFIINVDLTEEGLLHVEDI
ILHMFQYIQKLRAEGPQEWVFQELKDLNAVAFRFKDKERPRGYTSKIAGILHYYPLEEVL
TAEYLLEEFRPDLIEMVLDKLRPENVRVAIVSKSFEGKTDRTEEWYGTQYKQEAIPDEVI
KKWQNADLNGKFKLPTKNEFIPTNFEILPLEKEATPYPALIKDTAMSKLWFKQDDKFFLP
KANLNFEFFSPFAYVDPLHSNMAYLYLELLKDSLNEYAYAAELAGLSYDLQNTIYGMYLS
VKGYNDKQPILLKKIIEKMATFEIDEKRFEIIKEAYMRSLNNFRAEQPHQHAMYYLRLLM
TEVAWTKDELKEALDDVTLPRLKAFIPQLLSRLHIEALLHGNITKQAALGIMQMVEDTLI
EHAHTKPLLPSQLVRYREVQLPDRGWFVYQQRNEVHNNSGIEIYYQTDMQSTSENMFLEL
FAQIISEPAFNTLRTKEQLGYIVFSGPRRANGIQGLRFIIQSEKPPHYLESRVEAFLITM
EKSIEDMTEEAFQKHIQALAIRRLDKPKKLSAESAKYWGEIISQQYNFDRDNTEVAYLKT
LTKEDIIKFYKEMLAVDAPRRHKVSVHVLAREMDSNPVVGEFPAQNDINLSQAPALPQPE
VIQNMTEFKRGLPLFPLVKPHINFMAAKL

Ligands and cofactors

IDNameFormulaCopies
2QXmethyl [(2S)-2-(5-{5-[4-({(2S)-2-[(3S)-3-amino-2-oxopiperidin-1-yl]-2-cyclohexy…C44 H54 F N5 O42
ZNZinc ionZn2

Primary citation

Dual Exosite-binding Inhibitors of Insulin-degrading Enzyme Challenge Its Role as the Primary Mediator of Insulin Clearance in Vivo. Durham, T.B., Toth, J.L., Klimkowski, V.J. et al. J Biol Chem (2015) 290:20044-20059. DOI 10.1074/jbc.M115.638205 · 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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