Improved insulin stability through amino acid substitution.


Abstract

Insulin analogs designed to decrease self-association and increase absorption rates from subcutaneous tissue were found to have altered stability. Replacement of HB10 with aspartic acid increased stability while substitutions at B28 and/or B29 were either comparable to insulin or had decreased stability. The principal chemical degradation product of accelerated storage conditions was a disulfide-linked multimer that was formed through a disulfide interchange reaction which resulted from beta-elimination of the disulfides. The maintenance of the native state of insulin was shown to be important in protecting the disulfides from reduction by dithiothreitol and implicitly from the disulfide interchange reaction that occurs during storage. To understand how these amino acid changes alter chemical stability, the intramolecular conformational equilibria of each analog was assessed by equilibrium denaturation. The Gibbs free energy of unfolding was compared with the chemical stability during storage for over 20 analogs. A significant positive correlation (R2 = 0.8 and P less than 0.0005) exists between the conformational stability and chemical stability of these analogs, indicating that the chemical stability of insulin's disulfides is under the thermodynamic control of the conformational equilibria. Study holds ProTherm entries: 9845, 9846, 9847, 9848, 9849, 9850, 9851, 9852, 9853, 9854, 9855, 9856, 9857, 9858, 9859, 9860, 9861, 9862, 9863 Extra Details: additive : DTT(25 mM), amino acid substiution; insulin stability

Submission Details

ID: nxi2QUZe3

Submitter: Connie Wang

Submission Date: April 24, 2018, 8:38 p.m.

Version: 1

Publication Details
Brems DN;Brown PL;Bryant C;Chance RE;Green LK;Long HB;Miller AA;Millican R;Shields JE;Frank BH,Protein Eng. (1992) Improved insulin stability through amino acid substitution. PMID:1438162
Additional Information

Structure view and single mutant data analysis

Study data

No weblogo for data of varying length.
Colors: D E R H K S T N Q A V I L M F Y W C G P
 

Data Distribution

Studies with similar sequences (approximate matches)

Correlation with other assays (exact sequence matches)


Relevant PDB Entries

Structure ID Release Date Resolution Structure Title
1XGL 1997-04-01 HUMAN INSULIN DISULFIDE ISOMER, NMR, 10 STRUCTURES
2LWZ 2013-08-28 NMR Structures of Single-chain Insulin
1HIT 1994-01-31 Receptor binding redefined by a structural switch in a mutant Human Insulin
2AIY 2000-02-28 R6 HUMAN INSULIN HEXAMER (SYMMETRIC), NMR, 20 STRUCTURES
2MVC 2014-12-10 Solution structure of human insulin at pH 1.9
1MHJ 1995-10-15 SOLUTION STRUCTURE OF THE SUPERACTIVE MONOMERIC DES-[PHE(B25)] HUMAN INSULIN MUTANT. ELUCIDATION OF THE STRUCTURAL BASIS FOR THE MONOMERIZATION OF THE DES-[PHE(B25)] INSULIN AND THE DIMERIZATION OF NATIVE INSULIN
1T1P 2004-08-10 NMR STRUCTURE OF HUMAN INSULIN MUTANT HIS-B10-ASP, VAL-B12-THR, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES
2JMN 2006-12-05 NMR structure of human insulin mutant His-B10-Asp, Pro-B28-Lys, Lys-B29-Pro, 20 structures
5AIY 2000-02-28 R6 HUMAN INSULIN HEXAMER (SYMMETRIC), NMR, 'RED' SUBSTATE, AVERAGE STRUCTURE
2M1D 2013-02-27 Biosynthetic engineered B28K-B29P human insulin monomer structure in in water/acetonitrile solutions.
5MWQ 2018-02-14 Biosynthetic engineered A21K-B31K-B32R human insulin monomer structure in water/acetonitrile solution
2KJJ 2010-06-16 Dynamics of insulin probed by 1H-NMR amide proton exchange anomalous flexibility of the receptor-binding surface
1FUB 2000-10-16 FIRST PROTEIN STRUCTURE DETERMINED FROM X-RAY POWDER DIFFRACTION DATA
2KXK 2011-06-01 Human Insulin Mutant A22Gly-B31Lys-B32Arg
2N2X 2016-02-03 Solution structure of [GlyB24,B27-B29 triazole cross-linked]-insulin analogue at pH 1.9
3AIY 2000-02-28 R6 HUMAN INSULIN HEXAMER (SYMMETRIC), NMR, REFINED AVERAGE STRUCTURE
2MPG 2014-06-11 Solution structure of the [AibB8,LysB28,ProB29]-insulin analogue
1T0C 2005-08-16 Solution Structure of Human Proinsulin C-Peptide
1JCO 2001-10-03 Solution structure of the monomeric [Thr(B27)->Pro,Pro(B28)->Thr] insulin mutant (PT insulin)
1IOH 1999-01-13 INSULIN MUTANT A8 HIS,(B1, B10, B16, B27)GLU, DES-B30, NMR, 26 STRUCTURES
2JUV 2007-10-16 AbaA3-DKP-insulin
2M2M 2013-03-06 Structure of [L-HisB24] insulin analogue at pH 1.9
1K3M 2001-10-17 NMR STRUCTURE OF HUMAN INSULIN MUTANT ILE-A2-ALA, HIS-B10-ASP, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES
2RN5 2008-10-28 Humal Insulin Mutant B31Lys-B32Arg
5MIZ 2017-01-25 MD ensemble of bovine insulin
2JUM 2007-10-16 ThrA3-DKP-insulin
2L1Z 2011-08-31 NMR Structure of human insulin mutant GLY-B20-D-ALA, GLY-B23-D-ALA PRO-B28-LYS, LYS-B29-PRO, 20 Structures
1T1K 2004-08-10 NMR STRUCTURE OF HUMAN INSULIN MUTANT HIS-B10-ASP, VAL-B12-ALA, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES
3INS 1989-01-09 STRUCTURE OF INSULIN. RESULTS OF JOINT NEUTRON AND X-RAY REFINEMENT
4IDW 2013-06-05 Polycrystalline T6 Bovine Insulin: Anisotropic Lattice Evolution and Novel Structure Refinement Strategy
1MHI 1995-10-15 THREE-DIMENSIONAL SOLUTION STRUCTURE OF AN INSULIN DIMER. A STUDY OF THE B9(ASP) MUTANT OF HUMAN INSULIN USING NUCLEAR MAGNETIC RESONANCE DISTANCE GEOMETRY AND RESTRAINED MOLECULAR DYNAMICS
1HIQ 1994-01-31 PARADOXICAL STRUCTURE AND FUNCTION IN A MUTANT HUMAN INSULIN ASSOCIATED WITH DIABETES MELLITUS
2JZQ 2008-02-26 Design of an Active Ultra-Stable Single-Chain Insulin Analog 20 Structures
4AIY 2000-02-28 R6 HUMAN INSULIN HEXAMER (SYMMETRIC), NMR, 'GREEN' SUBSTATE, AVERAGE STRUCTURE
2L1Y 2011-08-31 NMR Structure of human insulin mutant GLY-B20-D-ALA, GLY-B23-D-ALA PRO-B28-LYS, LYS-B29-PRO, 20 Structures
2LGB 2012-04-11 Modified A22Gly-B31Arg Human Insulin
1VKT 1997-04-01 HUMAN INSULIN TWO DISULFIDE MODEL, NMR, 10 STRUCTURES
5WBT 2017-11-15 Solution Structure and Dynamics of an Ultra-Stable Single-Chain Insulin Analog STUDIES OF AN ENGINEERED MONOMER AND IMPLICATIONS FOR RECEPTOR BINDING
1KMF 2002-01-09 NMR STRUCTURE OF HUMAN INSULIN MUTANT ILE-A2-ALLO-ILE, HIS-B10-ASP, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES
1BZV 1999-05-18 [D-ALAB26]-DES(B27-B30)-INSULIN-B26-AMIDE A SUPERPOTENT SINGLE-REPLACEMENT INSULIN ANALOGUE, NMR, MINIMIZED AVERAGE STRUCTURE
2MPI 2014-12-24 Solution structure of B24G insulin
2M2N 2013-03-06 Structure of [L-HisB24] insulin analogue at pH 8.0
1A7F 1998-07-15 INSULIN MUTANT B16 GLU, B24 GLY, DES-B30, NMR, 20 STRUCTURES
2KQP 2010-01-26 NMR Structure of Proinsulin
1HO0 2000-12-20 NEW B-CHAIN MUTANT OF BOVINE INSULIN
5MHD 2017-08-09 Biosynthetic engineered A22S-B3K-B31R human insulin monomer structure in water/acetonitrile solutions.
2KJU 2010-06-16 NMR structure of human insulin mutant glu-b21-d-glu, his-b10 asp pro-b28-lys, lys-b29-pro, 20 structures
2N2V 2016-02-03 Solution structure of [B26-B29 triazole cross-linked]-insulin analogue at pH 1.9
1SJU 1998-03-18 MINI-PROINSULIN, SINGLE CHAIN INSULIN ANALOG MUTANT: DES B30, HIS(B 10)ASP, PRO(B 28)ASP AND PEPTIDE BOND BETWEEN LYS B 29 AND GLY A 1, NMR, 20 STRUCTURES
2M2O 2013-03-06 Structure of [D-HisB24] insulin analogue at pH 1.9
1SJT 1998-03-18 MINI-PROINSULIN, TWO CHAIN INSULIN ANALOG MUTANT: DES B30, HIS(B 10)ASP, PRO(B 28)ASP, NMR, 20 STRUCTURES
2HHO 2006-07-18 NMR structure of human insulin mutant GLY-B8-SER, HIS-B10-ASP PRO-B28-LYS, LYS-B29-PRO, 20 structures
2H67 2006-07-18 NMR structure of human insulin mutant HIS-B5-ALA, HIS-B10-ASP PRO-B28-LYS, LYS-B29-PRO, 20 structures
2N2W 2016-02-03 Solution structure of [B26-B29 triazole cross-linked]-insulin analogue at pH 8.0
1EFE 2000-03-17 AN ACTIVE MINI-PROINSULIN, M2PI
1AIY 1997-11-12 R6 HUMAN INSULIN HEXAMER (SYMMETRIC), NMR, 10 STRUCTURES
1IOG 1999-01-13 INSULIN MUTANT A3 GLY,(B1, B10, B16, B27)GLU, DES-B30, NMR, 19 STRUCTURES
1SF1 2004-03-30 NMR STRUCTURE OF HUMAN INSULIN under Amyloidogenic Condition, 15 STRUCTURES
1HUI 1997-03-12 INSULIN MUTANT (B1, B10, B16, B27)GLU, DES-B30, NMR, 25 STRUCTURES
2JUU 2007-10-16 allo-ThrA3 DKP-insulin
2M2P 2013-03-06 Structure of [D-HisB24] insulin analogue at pH 8.0
2K91 2008-11-18 Enhancing the activity of insulin by stereospecific unfolding
2HH4 2006-07-18 NMR structure of human insulin mutant GLY-B8-D-SER, HIS-B10-ASP PRO-B28-LYS, LYS-B29-PRO, 20 structures
1LKQ 2002-05-22 NMR STRUCTURE OF HUMAN INSULIN MUTANT ILE-A2-GLY, VAL-A3-GLY, HIS-B10-ASP, PRO-B28-LYS, LYS-B29-PRO, 20 STRUCTURES
2M1E 2013-02-27 Biosynthetic engineered B28K-B29P human insulin monomer structure in in water solutions.
2HIU 1997-04-01 NMR STRUCTURE OF HUMAN INSULIN IN 20% ACETIC ACID, ZINC-FREE, 10 STRUCTURES
1HLS 1995-09-15 NMR STRUCTURE OF THE HUMAN INSULIN-HIS(B16)
2MVD 2014-12-10 Solution structure of [GlnB22]-insulin mutant at pH 1.9
1HIS 1994-01-31 Structure and dynamics of des-pentapeptide-insulin in solution: the molten-globule hypothesis.
2K9R 2008-11-11 Enhancing the activity of insulin by stereospecific unfolding
2JV1 2007-12-11 NMR structure of human insulin monomer in 35% CD3CN zinc free, 50 structures
1AI0 1997-11-12 R6 HUMAN INSULIN HEXAMER (NON-SYMMETRIC), NMR, 10 STRUCTURES
1FU2 2000-10-16 FIRST PROTEIN STRUCTURE DETERMINED FROM X-RAY POWDER DIFFRACTION DATA
2KQQ 2010-11-24 NMR structure of human insulin mutant gly-b8-d-ala, his-b10-asp, pro-b28-lys, lys-b29-pro, 20 structures
2MLI 2014-08-20 NMR structure of B25-(alpha, beta)-dehydro-phenylalanine insulin
1T1Q 2004-08-10 NMR STRUCTURE OF HUMAN INSULIN MUTANT HIS-B10-ASP, VAL-B12-ABA, PRO-B28-LYS, LYS-B29-PRO, 15 STRUCTURES
3W7Y 2013-07-03 0.92 0.92A structure of 2Zn human insulin at 100K
5E7W 2016-10-12 0.95 X-ray Structure of Human Recombinant 2Zn insulin at 0.92 Angstrom
5HQI 2017-01-25 0.97 Insulin with proline analog HzP at position B28 in the T2 state
1MSO 2003-03-04 1.0 T6 Human Insulin at 1.0 A Resolution
3HYD 2009-10-06 1.0 LVEALYL peptide derived from human insulin chain B, residues 11-17
4FKA 2013-02-13 1.08 High resolution structure of the manganese derivative of insulin
3TT8 2011-10-19 1.12 Crystal Structure Analysis of Cu Human Insulin Derivative
3W7Z 2013-07-03 1.15 1.15A structure of human 2Zn insulin at 293K
4IHN 2013-12-25 1.16 High Resolution Insulin by Langmuir-Blodgett Modified Hanging Drop Vapour Diffusion
5USP 2018-02-21 1.17 Insulin with proline analog Pip at position B28 in the T2 state
5UOZ 2018-02-07 1.17 Insulin with proline analog FyP at position B28 in the T2 state
5URT 2018-02-14 1.18 Insulin with proline analog DhP at position B28 in the T2 state
1G7A 2001-08-03 1.2 1.2 A structure of T3R3 human insulin at 100 K
4AJX 2013-01-09 1.2 Ligand controlled assembly of hexamers, dihexamers, and linear multihexamer structures by an engineered acylated insulin
1M5A 2002-08-14 1.2 Crystal Structure of 2-Co(2+)-Insulin at 1.2A Resolution
5UU2 2018-02-21 1.22 Insulin with proline analog ThioP at position B28 in the T2 state
6GV0 2019-07-03 1.26 Insulin glulisine
5HRQ 2017-01-25 1.28 Insulin with proline analog HzP at position B28 in the R6 state
4E7U 2012-04-04 1.3 The structure of T3R3 bovine insulin
1PID 1996-12-07 1.3 BOVINE DESPENTAPEPTIDE INSULIN
5USV 2018-02-21 1.3 Insulin with proline analog AzeP at position B28 in the T2 state
1G7B 2001-08-03 1.3 1.3 A STRUCTURE OF T3R3 HUMAN INSULIN AT 100 K
3BXQ 2008-05-20 1.3 The structure of a mutant insulin uncouples receptor binding from protein allostery. An electrostatic block to the TR transition
5UQA 2018-02-21 1.31 Insulin with proline analog FzP at position B28 in the R6 state
5HPR 2017-01-25 1.33 Insulin with proline analog HyP at position B28 in the T2 state
6S34 2019-07-03 1.35 Zinc free, dimeric human insulin determined to 1.35 Angstrom resolution
3EXX 2009-05-19 1.35 Structure of the T6 human insulin derivative with nickel at 1.35 A resolution
3FQ9 2009-08-04 1.35 Design of an insulin analog with enhanced receptor-binding selectivity. Rationale, structure, and therapeutic implications
5UDP 2017-01-11 1.35 High resolution x-ray crystal structure of synthetic insulin lispro
5ENA 2016-01-13 1.35 Xray crystal structure of isotope-labeled human insulin
2OMH 2007-03-27 1.36 Structure of human insulin cocrystallized with ARG-12 peptide in presence of urea
4CY7 2014-05-28 1.4 Crystal structure of human insulin analogue (NMe-AlaB8)-insulin crystal form II
4NIB 2014-08-27 1.4 Crystal structure of human insulin mutant B20 D-ala, B23 D-ala
4E7T 2012-04-04 1.4 The structure of T6 bovine insulin
1BEN 1996-07-11 1.4 INSULIN COMPLEXED WITH 4-HYDROXYBENZAMIDE
3W80 2013-07-03 1.4 Crystal structure of dodecamer human insulin with double C-axis length of the hexamer 2 Zn insulin cell
2BN1 2005-09-07 1.4 Insulin after a high dose x-ray burn
2BN3 2005-09-07 1.4 Insulin before a high dose x-ray burn
5AZZ 2017-05-03 1.45 Crystal structure of seleno-insulin
4M4L 2014-01-15 1.45 The structure of Cu T6 bovine insulin
4EY9 2013-05-01 1.47 Human Insulin
4EYD 2013-05-01 1.47 Human Insulin
4EY1 2013-05-01 1.47 Human Insulin
2WRX 2010-02-09 1.5 Semi-synthetic analogue of human insulin NMeAlaB26-insulin at pH 3.0
5D54 2016-01-13 1.5 In meso X-ray crystallography structure of insulin at 100 K
4XC4 2015-02-11 1.5 Insulin co-crystallizes in the presence of it beta-cell chaperone sulfatide
4M4M 2014-01-15 1.5 The structure of Ni T6 bovine insulin
1ZNI 1998-01-28 1.5 INSULIN
2WS6 2010-02-09 1.5 Semi-synthetic analogue of human insulin NMeTyrB26-insulin in hexamer form
5D53 2016-01-13 1.5 In meso in situ serial X-ray crystallography structure of insulin at 100 K
4CXL 2014-05-28 1.5 Human insulin analogue (D-ProB8)-insulin
4INS 1990-04-15 1.5 THE STRUCTURE OF 2ZN PIG INSULIN CRYSTALS AT 1.5 ANGSTROMS RESOLUTION
4P65 2014-10-22 1.5 Crystal structure of an cyclohexylalanine substituted insulin analog.
1ZEH 1998-12-09 1.5 STRUCTURE OF INSULIN
2C8R 2006-03-08 1.5 insuline(60sec) and UV laser excited fluorescence
5EN9 2016-01-13 1.5 High resolution x-ray crystal structure of isotope-labeled ester-insulin
2OMG 2007-03-27 1.52 Structure of human insulin cocrystallized with protamine and urea
4EYN 2013-05-01 1.53 Human Insulin
5BQQ 2016-02-03 1.54 Human insulin with intra-chain chemical crosslink between modified B27 and B30
4EXX 2013-05-01 1.55 Human Insulin
5T7R 2017-12-06 1.55 A6-A11 trans-dicarba human insulin
2WRU 2010-02-09 1.57 Semi-synthetic highly active analogue of human insulin NMeAlaB26-DTI- NH2
4UNE 2014-10-15 1.59 Human insulin B26Phe mutant crystal structure
4F1B 2013-05-08 1.59 Human Insulin
4EYP 2013-05-01 1.59 Human Insulin
4IUZ 2013-02-13 1.6 High resolution crystal structure of racemic ester insulin
3E7Y 2009-02-24 1.6 Structure of human insulin
1UZ9 2005-03-03 1.6 Crystallographic and solution studies of N-lithocholyl insulin: a new generation of prolonged-acting insulins.
3I3Z 2010-01-05 1.6 Human insulin
3ZU1 2011-08-03 1.6 Structure of LysB29(Nepsilon omega-carboxyheptadecanoyl) des(B30) Human Insulin
1TRZ 1994-01-31 1.6 CRYSTALLOGRAPHIC EVIDENCE FOR DUAL COORDINATION AROUND ZINC IN THE T3R3 HUMAN INSULIN HEXAMER
2WS1 2010-02-09 1.6 Semi-synthetic analogue of human insulin NMeTyrB26-insulin in monomer form
1ZEG 1998-07-15 1.6 STRUCTURE OF B28 ASP INSULIN IN COMPLEX WITH PHENOL
1DEI 1997-06-16 1.6 DESHEPTAPEPTIDE (B24-B30) INSULIN
1GUJ 2002-03-08 1.62 Insulin at pH 2: structural analysis of the conditions promoting insulin fibre formation.
4F51 2013-05-15 1.64 Human Insulin
4F4T 2013-05-15 1.64 Human Insulin
4F4V 2013-05-15 1.64 Human Insulin
4F1D 2013-05-08 1.64 Human Insulin
4F1G 2013-05-08 1.64 Human insulin
6QQ7 2019-02-27 1.65 Bovine insulin at ambient pressure
1SDB 1997-02-12 1.65 PORCINE DESB1-2 DESPENTAPEPTIDE(B26-B30) INSULIN
4EX1 2013-05-01 1.66 Human Insulin
4IYD 2014-02-12 1.66 Insulin glargine crystal structure 1
4F0O 2013-05-08 1.67 Human Insulin
3UTQ 2012-01-25 1.67 Human HLA-A*0201-ALWGPDPAAA
4F8F 2013-05-22 1.68 Human Insulin
4F1F 2013-05-08 1.68 Human Insulin
4F0N 2013-05-08 1.68 Human Insulin
5C0D 2016-05-04 1.68 HLA-A02 carrying AQWGPDPAAA
5VIZ 2017-10-18 1.7 X-Ray structure of Insulin Glargine
1B17 2003-04-08 1.7 PH AFFECTS GLU B13 SWITCHING AND SULFATE BINDING IN CUBIC INSULIN CRYSTALS (PH 5.00 COORDINATES)
2OLZ 2007-12-04 1.7 Structure of human insulin in presence of thiocyanate at pH 7.0
4F1C 2013-05-08 1.7 Human Insulin
1B2A 2003-04-08 1.7 PH AFFECTS GLU B13 SWITCHING AND SULFATE BINDING IN CUBIC INSULIN CRYSTALS (PH 6.00 COORDINATES)
5CNY 2015-08-26 1.7 Crystal Structure of human zinc insulin at pH 5.5
3ZI3 2013-03-06 1.7 Crystal structure of the B24His-insulin - human analogue
9INS 1991-11-07 1.7 MONOVALENT CATION BINDING IN CUBIC INSULIN CRYSTALS
1B2D 2003-04-08 1.7 PH AFFECTS GLU B13 SWITCHING AND SULFATE BINDING IN CUBIC INSULIN CRYSTALS (PH 6.35 COORDINATES)
4CXN 2014-05-28 1.7 Crystal structure of human insulin analogue (NMe-AlaB8)-insulin crystal form I
3E7Z 2009-02-24 1.7 Structure of human insulin
5CO2 2015-08-26 1.7 Crystalization of human zinc insulin at pH 5.5
5BOQ 2016-02-03 1.7 Human insulin with intra-chain chemical crosslink between modified B24 and B29
2OLY 2007-12-04 1.7 Structure of human insulin in presence of urea at pH 7.0
4RXW 2015-01-21 1.73 Crystal Structure of the cobalt human insulin derivative
5BTS 2016-03-09 1.77 Structural and biophysical characterization of a covalent insulin dimer formed during storage of neutral formulation of human insulin
4GBC 2013-06-12 1.78 Crystal structure of aspart insulin at pH 6.5
1EV3 2000-12-04 1.78 Structure of the rhombohedral form of the M-cresol/insulin R6 hexamer
4EWZ 2013-05-01 1.79 Human Insulin
4IYF 2014-02-12 1.8 Insulin glargine crystal structure 2
4I5Y 2013-11-20 1.8 Insulin protein crystallization via langmuir-blodgett
4F1A 2013-05-08 1.8 Human Insulin
6P4Z 2019-06-12 1.8 Structure of gadolinium-caged cobalt (III) insulin hexamer
3RTO 2011-05-18 1.8 Acoustically mounted porcine insulin microcrystals yield an X-ray SAD structure
2CEU 2006-03-03 1.8 Despentapeptide insulin in acetic acid (pH 2)
2G4M 2007-02-20 1.8 Insulin collected at 2.0 A wavelength
1RWE 2005-02-15 1.8 Enhancing the activity of insulin at receptor edge: crystal structure and photo-cross-linking of A8 analogues
1B2C 2003-04-08 1.8 PH AFFECTS GLU B13 SWITCHING AND SULFATE BINDING IN CUBIC INSULIN CRYSTALS (PH 6.26 COORDINATES)
1B18 2003-04-08 1.8 PH AFFECTS GLU B13 SWITCHING AND SULFATE BINDING IN CUBIC INSULIN CRYSTALS (PH 5.53 COORDINATES)
1B2G 2003-04-08 1.8 PH AFFECTS GLU B13 SWITCHING AND SULFATE BINDING IN CUBIC INSULIN CRYSTALS (PH 9.00 COORDINATES)
4AJZ 2013-01-09 1.8 Ligand controlled assembly of hexamers, dihexamers, and linear multihexamer structures by an engineered acylated insulin
1B19 2003-04-08 1.8 PH AFFECTS GLU B13 SWITCHING AND SULFATE BINDING IN CUBIC INSULIN CRYSTALS (PH 5.80 COORDINATES)
5CO6 2015-08-26 1.8 Crystal structure of human zinc insulin at pH 6.5
2VJZ 2008-09-16 1.8 Crystal structure form ultalente insulin microcrystals
4I5Z 2013-11-20 1.8 Insulin protein crystallization via langmuir-blodgett
1B2B 2003-04-08 1.8 PH AFFECTS GLU B13 SWITCHING AND SULFATE BINDING IN CUBIC INSULIN CRYSTALS (PH 6.16 COORDINATES)
2TCI 1996-01-29 1.8 X-RAY CRYSTALLOGRAPHIC STUDIES ON HEXAMERIC INSULINS IN THE PRESENCE OF HELIX-STABILIZING AGENTS, THIOCYANATE, METHYLPARABEN AND PHENOL
4E7V 2012-04-04 1.8 The structure of R6 bovine insulin
3GKY 2009-03-24 1.8 The Structural Basis of an ER Stress-Associated Bottleneck in a Protein Folding Landscape
5D52 2016-01-13 1.8 In meso in situ serial X-ray crystallography structure of insulin at room temperature
1XDA 1997-07-07 1.8 STRUCTURE OF INSULIN
4UNG 2014-10-15 1.81 Human insulin B26Asn mutant crystal structure
3I40 2010-01-05 1.85 Human insulin
4Z77 2015-06-24 1.85 Weak TCR binding to an unstable insulin epitope drives type 1 diabetes
3INC 2010-08-18 1.85 Crystal structure of human insulin with Ni+2 complex
4A7E 2011-11-30 1.86 X-ray crystal structure of porcine insulin flash-cooled at high pressure
4EX0 2013-05-01 1.86 Human Insulin
4GBN 2013-06-12 1.87 Crystal structure of aspart insulin at pH 6.5
4Z76 2015-06-24 1.88 Weak TCR binding to an unstable insulin epitope drives type 1 diabetes
5MT9 2017-04-05 1.88 Human insulin in complex with serotonin and arginine
3KQ6 2010-02-23 1.9 Enhancing the Therapeutic Properties of a Protein by a Designed Zinc-Binding Site, Structural principles of a novel long-acting insulin analog
1DPH 1993-01-15 1.9 CONFORMATIONAL CHANGES IN CUBIC INSULIN CRYSTALS IN THE PH RANGE 7-11
3ZQR 2011-08-24 1.9 NMePheB25 insulin analogue crystal structure
5BPO 2016-02-03 1.9 Human insulin with intra-chain chemical crosslink between modified B27 and B29
4M4J 2014-01-15 1.9 Radiation damage study of Cu T6-insulin - 0.30 MGy
1B2F 2003-04-08 1.9 PH AFFECTS GLU B13 SWITCHING AND SULFATE BINDING IN CUBIC INSULIN CRYSTALS (PH 6.98 COORDINATES)
1TYL 1994-09-30 1.9 THE STRUCTURE OF A COMPLEX OF HEXAMERIC INSULIN AND 4'-HYDROXYACETANILIDE
3MTH 1996-01-29 1.9 X-RAY CRYSTALLOGRAPHIC STUDIES ON HEXAMERIC INSULINS IN THE PRESENCE OF HELIX-STABILIZING AGENTS, THIOCYANATE, METHYLPARABEN AND PHENOL
1CPH 1993-01-15 1.9 CONFORMATIONAL CHANGES IN CUBIC INSULIN CRYSTALS IN THE PH RANGE 7-11
1B2E 2003-04-08 1.9 PH AFFECTS GLU B13 SWITCHING AND SULFATE BINDING IN CUBIC INSULIN CRYSTALS (PH 6.50 COORDINATES)
4M4H 2014-01-15 1.9 Radiation damage study of Cu T6-insulin - 0.06 MGy
1TYM 1994-09-30 1.9 THE STRUCTURE OF A COMPLEX OF HEXAMERIC INSULIN AND 4'-HYDROXYACETANILIDE
2WS4 2010-02-09 1.9 Semi-synthetic analogue of human insulin ProB26-DTI in monomer form
1ZEI 1999-02-16 1.9 CROSS-LINKED B28 ASP INSULIN
1EV6 2000-12-04 1.9 Structure of the monoclinic form of the M-cresol/insulin R6 hexamer
4M4I 2014-01-15 1.9 Radiation damage study of Cu T6-insulin - 0.12 MGy
4M4F 2014-01-15 1.9 Radiation damage study of Cu T6-insulin - 0.01 MGy
1HTV 2001-05-23 1.9 CRYSTAL STRUCTURE OF DESTRIPEPTIDE (B28-B30) INSULIN
5FB6 2016-06-15 1.9 Room-temperature macromolecular crystallography using a micro-patterned silicon chip with minimal background scattering
3ILG 2010-08-11 1.9 Crystal structure of humnan insulin Sr+2 complex
1EVR 2000-12-04 1.9 The structure of the resorcinol/insulin R6 hexamer
5CO9 2015-08-26 1.92 Crystal structure of human zinc insulin at pH 6.5
2C8Q 2006-03-08 1.95 insuline(1sec) and UV laser excited fluorescence
1OS3 2003-07-29 1.95 Dehydrated T6 human insulin at 100 K
5UU4 2018-02-21 1.97 Insulin with proline analog ThioP at position B28 in the R6 state
2OM1 2007-12-04 1.97 Structure of human insulin in presence of thiocyanate at pH 6.5
3ZS2 2011-08-31 1.97 TyrB25,NMePheB26,LysB28,ProB29-insulin analogue crystal structure
4EFX 2013-03-06 1.98 Highly biologically active insulin with additional disulfide bond
3U4N 2012-04-11 1.98 A novel covalently linked insulin dimer
3P2X 2011-11-23 2.0 Insulin fibrillation is the Janus face of induced fit. A chiaral clamp stabilizes the native state at the expense of activity
7INS 1994-01-31 2.0 STRUCTURE OF PORCINE INSULIN COCRYSTALLIZED WITH CLUPEINE Z
1Q4V 2003-08-19 2.0 CRYSTAL STRUCTURE OF ALLO-ILEA2-INSULIN, AN INACTIVE CHIRAL ANALOGUE: IMPLICATIONS FOR THE MECHANISM OF RECEPTOR
1ZNJ 1998-01-28 2.0 INSULIN, MONOCLINIC CRYSTAL FORM
2OMQ 2007-01-30 2.0 VEALYL peptide derived from human insulin chain B, residues 12-17
2W44 2009-12-22 2.0 Structure DeltaA1-A4 insulin
3V19 2012-12-12 2.0 Forestalling insulin fibrillation by insertion of a chiral clamp mechanism-based application of protein engineering to global health
1APH 1993-01-15 2.0 CONFORMATIONAL CHANGES IN CUBIC INSULIN CRYSTALS IN THE PH RANGE 7-11
6INS 1994-01-31 2.0 X-RAY ANALYSIS OF THE SINGLE CHAIN B29-A1 PEPTIDE-LINKED INSULIN MOLECULE. A COMPLETELY INACTIVE ANALOGUE
4FG3 2013-06-12 2.0 Crystal Structure Analysis of the Human Insulin
1BPH 1993-01-15 2.0 CONFORMATIONAL CHANGES IN CUBIC INSULIN CRYSTALS IN THE PH RANGE 7-11
2R36 2008-09-02 2.0 Crystal structure of ni human ARG-insulin
1IZB 1993-10-31 2.0 ROLE OF B13 GLU IN INSULIN ASSEMBLY: THE HEXAMER STRUCTURE OF RECOMBINANT MUTANT (B13 GLU-> GLN) INSULIN
2QIU 2008-02-26 2.0 Structure of Human Arg-Insulin
3FHP 2009-10-20 2.0 A neutron crystallographic analysis of a porcine 2Zn insulin at 2.0 A resolution
1QIZ 1999-06-22 2.0 HUMAN INSULIN HEXAMERS WITH CHAIN B HIS MUTATED TO TYR COMPLEXED WITH RESORCINOL
1J73 2001-05-30 2.0 Crystal structure of an unstable insulin analog with native activity.
4AKJ 2013-01-09 2.01 Ligand controlled assembly of hexamers, dihexamers, and linear multihexamer structures by an engineered acylated insulin
5MT3 2017-04-05 2.02 Human insulin in complex with serotonin and arginine
2OM0 2007-12-04 2.05 Structure of human insulin in presence of urea at pH 6.5
3Q6E 2011-04-20 2.05 Human insulin in complex with cucurbit[7]uril
5USS 2018-02-21 2.06 Insulin with proline analog PiP at position B28 in the R6 state
2R35 2008-09-02 2.08 Crystal structure of RB human arg-insulin
1W8P 2005-02-03 2.08 Structural properties of the B25Tyr-NMe-B26Phe insulin mutant.
6QRK 2019-03-06 2.1 High pressure structure of bovine insulin (200 MPa)
3T2A 2011-12-28 2.1 TMAO-grown cubic insulin (porcine)
2WS0 2010-02-09 2.1 Semi-synthetic analogue of human insulin NMeAlaB26-insulin at pH 7.5
6QQG 2019-03-06 2.15 High pressure structure of bovine insulin (60 MPa)
2WRV 2010-02-09 2.15 Semi-synthetic highly active analogue of human insulin NMeHisB26-DTI- NH2
6QRH 2019-02-27 2.15 High pressure structure of bovine insulin (100 MPa)
5HPU 2017-01-25 2.2 Insulin with proline analog HyP at position B28 in the R6 state
3IR0 2010-09-01 2.2 Crystal Structure of Human Insulin complexed with Cu+2 metal ion
4EWX 2013-05-01 2.2 Human Insulin
5MAM 2017-04-05 2.2 Human insulin in complex with serotonin
6GNQ 2019-06-12 2.2 Monoclinic crystalline form of human insulin, complexed with meta-cresol
3V1G 2012-12-12 2.2 Forestalling insulin fibrillation by insertion of a chiral clamp mechanism-based application of protein engineering to global health
2G56 2006-10-24 2.2 crystal structure of human insulin-degrading enzyme in complex with insulin B chain
2VK0 2008-09-16 2.2 Crystal structure form ultalente insulin microcrystals
2OMI 2007-03-27 2.24 Structure of human insulin cocrystallized with protamine
2G54 2006-10-24 2.25 Crystal structure of Zn-bound human insulin-degrading enzyme in complex with insulin B chain
2R34 2008-09-02 2.25 Crystal structure of MN human arg-insulin
6CK2 2018-06-13 2.25 Insulin analog containing a YB26W mutation
2A3G 2005-10-25 2.25 The structure of T6 bovine insulin
5UU3 2018-02-21 2.25 Insulin with proline analog DfP at position B28 in the R6 state
1OS4 2003-07-29 2.25 Dehydrated T6 human insulin at 295 K
4AK0 2013-01-09 2.28 Ligand controlled assembly of hexamers, dihexamers, and linear multihexamer structures by an engineered acylated insulin
5LIS 2016-08-03 2.29 Insulin solved by Native SAD from a dataset collected in one second
4BS3 2013-07-17 2.3 Bovin insulin structure determined by in situ crystal analysis and sulfur-SAD phasing at room temperature
1LPH 1996-06-20 2.3 LYS(B28)PRO(B29)-HUMAN INSULIN
5EMS 2016-11-16 2.3 Crystal Structure of an iodinated insulin analog
1XW7 2005-04-12 2.3 Diabetes-Associated Mutations in Human Insulin: Crystal Structure and Photo-Cross-Linking Studies of A-Chain Variant Insulin Wakayama
3ROV 2012-05-02 2.3 Insulin's biosynthesis and activity have opposing structural requirements: a new factor in neonatal diabetes mellitus
4EWW 2013-05-01 2.3 Human Insulin
1MPJ 1996-01-29 2.3 X-RAY CRYSTALLOGRAPHIC STUDIES ON HEXAMERIC INSULINS IN THE PRESENCE OF HELIX-STABILIZING AGENTS, THIOCYANATE, METHYLPARABEN AND PHENOL
4Z78 2015-06-24 2.3 Weak TCR binding to an unstable insulin epitope drives type 1 diabetes
1QIY 1999-06-22 2.3 HUMAN INSULIN HEXAMERS WITH CHAIN B HIS MUTATED TO TYR COMPLEXED WITH PHENOL
3P33 2011-11-23 2.3 Insulin fibrillation is the Janus face of induced fit. A chiral clamp stabilizes the native state at the expense of activity
4WDI 2015-06-24 2.31 Weak TCR binding to an unstable insulin epitope drives type 1 diabetes
3WS3 2014-03-26 2.34 Crystal Structure of H-2D in complex with an insulin derived peptide
1QJ0 1999-06-22 2.4 HUMAN INSULIN HEXAMERS WITH CHAIN B HIS MUTATED TO TYR
1JK8 2001-08-22 2.4 Crystal structure of a human insulin peptide-HLA-DQ8 complex
4GBK 2013-06-12 2.4 Crystal structure of aspart insulin at pH 8.5
2WRW 2010-02-09 2.41 Semi-synthetic highly active analogue of human insulin D-ProB26-DTI- NH2
5URU 2018-02-21 2.41 Insulin with proline analog DhP at position B28 in the R6 state
5D5E 2016-01-13 2.41 In meso in situ serial X-ray crystallography structure of insulin by sulfur-SAD at 100 K
1B9E 1999-11-17 2.5 HUMAN INSULIN MUTANT SERB9GLU
4Y19 2015-09-23 2.5 immune complex
2ZPP 2008-10-28 2.5 Neutron crystal structure of cubic insulin at pD9
4GBI 2013-06-12 2.5 Crystal structure of aspart insulin at pH 6.5
1IZA 1993-10-31 2.5 ROLE OF B13 GLU IN INSULIN ASSEMBLY: THE HEXAMER STRUCTURE OF RECOMBINANT MUTANT (B13 GLU-> GLN) INSULIN
4GBL 2013-06-12 2.5 Crystal structure of aspart insulin at pH 8.5
1JCA 2001-06-20 2.5 Non-standard Design of Unstable Insulin Analogues with Enhanced Activity
2INS 1982-08-05 2.5 THE STRUCTURE OF DES-PHE B1 BOVINE INSULIN
3JSD 2010-09-15 2.5 Insulin's biosynthesis and activity have opposing structural requirements: a new factor in neonatal diabetes mellitus
1WAV 1997-02-28 2.5 CRYSTAL STRUCTURE OF FORM B MONOCLINIC CRYSTAL OF INSULIN
2ZP6 2008-07-22 2.56 Crystal structure of Bovine Insulin (Hexameric form)
2WS7 2010-02-09 2.59 Semi-synthetic analogue of human insulin ProB26-DTI
3UTT 2012-01-25 2.6 1E6-A*0201-ALWGPDPAAA Complex, Triclinic
2WBY 2009-03-24 2.6 Crystal structure of human insulin-degrading enzyme in complex with insulin
2EFA 2008-01-22 2.7 Neutron crystal structure of cubic insulin at pD6.6
3UTS 2012-01-25 2.71 1E6-A*0201-ALWGPDPAAA Complex, Monoclinic
4UNH 2014-10-15 2.75 Human insulin B26Gly mutant crystal structure
2WC0 2009-03-24 2.8 crystal structure of human insulin degrading enzyme in complex with iodinated insulin
5WDM 2017-11-15 2.8 An ultra-stable single-chain insulin analog resists thermal inactivation and exhibits biological signaling duration equivalent to the native protein
5HYJ 2016-05-04 3.06 1E6 TCR in Complex with HLA-A02 carrying AQWGPDPAAA
6HN5 2018-11-21 3.2 Leucine-zippered human insulin receptor ectodomain with single bound insulin - 'upper' membrane-distal part
5CJO 2016-07-20 3.29 Crystal Structure Analysis of Elbow-Engineered-Fab-Bound Human Insulin Degrading Enzyme (IDE) in Complex with Insulin
4OGA 2014-08-27 3.5 Insulin in complex with Site 1 of the human insulin receptor
6BFC 2017-12-27 3.7 Cryo-EM structure of human insulin degrading enzyme in complex with insulin
6B70 2017-12-27 3.7 Cryo-EM structure of human insulin degrading enzyme in complex with FAB H11-E heavy chain, FAB H11-E light chain and insulin
6B3Q 2017-11-22 3.7 Cryo-EM structure of human insulin degrading enzyme in complex with insulin
3W11 2013-01-09 3.9 Insulin receptor ectodomain construct comprising domains L1-CR in complex with human insulin, Alpha-CT peptide(704-719) and FAB 83-7
5WOB 2018-04-18 3.95 Crystal Structure Analysis of Fab1-Bound Human Insulin Degrading Enzyme (IDE) in Complex with Insulin
4Y1A 2015-09-23 4.0 immune complex
6CE9 2018-03-14 4.3 Insulin Receptor ectodomain in complex with two insulin molecules
3W13 2013-01-09 4.3 Insulin receptor ectodomain construct comprising domains L1-CR in complex with high-affinity insulin analogue [D-PRO-B26]-DTI-NH2, alphact peptide(693-719) and FAB 83-7
3W12 2013-01-09 4.3 Insulin receptor ectodomain construct comprising domains L1-CR in complex with high-affinity insulin analogue [D-PRO-B26]-DTI-NH2, alpha-CT peptide(704-719) and FAB 83-7
5KQV 2017-07-19 4.4 Insulin receptor ectodomain construct comprising domains L1,CR,L2, FnIII-1 and alphaCT peptide in complex with bovine insulin and FAB 83-14 (REVISED STRUCTURE)
6CEB 2018-03-14 4.7 Insulin Receptor ectodomain in complex with two insulin molecules - C1 symmetry
6CE7 2018-03-14 7.4 Insulin Receptor ectodomain in complex with one insulin molecule

Relevant UniProtKB Entries

Percent Identity Matching Chains Protein Accession Entry Name
547.8 B,D,F,H,J,L Insulin P01338 INS2_BATSP
550.2 B,D,F,H,J,L Insulin P68987 INS_PETMA
550.2 B,D,F,H,J,L Insulin P68988 INS_LAMFL
555.6 B,D,F,H,J,L Insulin C0HJI7 INS1_HUSDA
553.8 B,D,F,H,J,L Insulin C0HJI3 INS2_KATPE
553.8 B,D,F,H,J,L Insulin P09476 INS_ATRSP
553.8 B,D,F,H,J,L Insulin Q9W7R2 INS_VERMO
553.8 B,D,F,H,J,L Insulin P09477 INS_PLAFE
553.8 B,D,F,H,J,L Insulin P04667 INS_ONCKE
555.6 B,D,F,H,J,L Insulin P01340 INS_KATPE
558.6 B,D,F,H,J,L Insulin P83770 INSL_VIGUN
555.6 B,D,F,H,J,L Insulin P12707 INS2_XENLA
577.2 B,D,F,H,J,L Insulin C0HJI8 INS2_HUSDA
579.6 B,D,F,H,J,L Insulin P21563 INS_RODSP
600.0 B,D,F,H,J,L Insulin P81423 INS_ACIGU
557.4 B,D,F,H,J,L Insulin P12706 INS1_XENLA
577.8 B,D,F,H,J,L Insulin P69048 INS_TRASC
577.8 B,D,F,H,J,L Insulin P69047 INS_TRADO
577.8 B,D,F,H,J,L Insulin P67969 INS_STRCA
577.8 B,D,F,H,J,L Insulin P67968 INS_MELGA
577.8 B,D,F,H,J,L Insulin P67970 INS_CHICK
1149.6000000000001 A,B,C,D,E,F,G,H,I,J,K,L Insulin P01323 INS2_RAT
1149.6000000000001 A,B,C,D,E,F,G,H,I,J,K,L Insulin P01326 INS2_MOUSE
578.4 B,D,F,H,J,L Insulin P51463 INS_SELRF
578.4 B,D,F,H,J,L Insulin P68243 INS_CAIMO
578.4 B,D,F,H,J,L Insulin P68245 INS_ANSAN
578.4 B,D,F,H,J,L Insulin P01333 INS_ANAPL
1143.0 A,B,C,D,E,F,G,H,I,J,K,L Insulin P18109 INS_DIDVI
559.8 B,D,F,H,J,L Insulin P67971 INS_SAISC
559.8 B,D,F,H,J,L Insulin P67972 INS_AOTTR
1122.6 A,B,C,D,E,F,G,H,I,J,K,L Insulin P01320 INS_CAMDR
1131.0 A,B,C,D,E,F,G,H,I,J,K,L Insulin P01324 INS_ACOCA
600.0 B,D,F,H,J,L Insulin P01318 INS_SHEEP
1171.2 A,B,C,D,E,F,G,H,I,J,K,L Insulin Q62587 INS_PSAOB
1200.0 A,B,C,D,E,F,G,H,I,J,K,L Insulin P01315 INS_PIG
1200.0 A,B,C,D,E,F,G,H,I,J,K,L Insulin P67974 INS_PHYMC
1171.2 A,B,C,D,E,F,G,H,I,J,K,L Insulin P01310 INS_HORSE
600.0 B,D,F,H,J,L Insulin P06306 INS_FELCA
600.0 B,D,F,H,J,L Insulin P01319 INS_CAPHI
1200.0 A,B,C,D,E,F,G,H,I,J,K,L Insulin P01321 INS_CANLF
1143.0 A,B,C,D,E,F,G,H,I,J,K,L Insulin P01317 INS_BOVIN
1200.0 A,B,C,D,E,F,G,H,I,J,K,L Insulin P67973 INS_BALPH
1143.0 A,B,C,D,E,F,G,H,I,J,K,L Insulin P01314 INS_BALBO
1180.2 A,B,C,D,E,F,G,H,I,J,K,L Insulin P01311 INS_RABIT
1180.2 A,B,C,D,E,F,G,H,I,J,K,L Insulin Q91XI3 INS_ICTTR
1151.4000000000003 A,B,C,D,E,F,G,H,I,J,K,L Insulin P01313 INS_CRILO
1200.0 A,B,C,D,E,F,G,H,I,J,K,L Insulin Q8HXV2 INS_PONPY
1200.0 A,B,C,D,E,F,G,H,I,J,K,L Insulin P30410 INS_PANTR
1200.0 A,B,C,D,E,F,G,H,I,J,K,L Insulin P30406 INS_MACFA
1200.0 A,B,C,D,E,F,G,H,I,J,K,L Insulin P01308 INS_HUMAN
1200.0 A,B,C,D,E,F,G,H,I,J,K,L Insulin Q6YK33 INS_GORGO
1143.0 A,B,C,D,E,F,G,H,I,J,K,L Insulin P01316 INS_ELEMA
1200.0 A,B,C,D,E,F,G,H,I,J,K,L Insulin P30407 INS_CHLAE
600.0 B,D,F,H,J,L Insulin F8WCM5 INSR2_HUMAN
543.0 A,C,E,G,I,K Insulin P01327 INS_CHICH
571.2 A,C,E,G,I,K Insulin P01322 INS1_RAT
571.2 A,C,E,G,I,K Insulin P01325 INS1_MOUSE