PDBsum entry 1xgl

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protein Protein-protein interface(s) links
Hormone PDB id
Protein chains
21 a.a.
30 a.a. *
* Residue conservation analysis
PDB id:
Name: Hormone
Title: Human insulin disulfide isomer, nmr, 10 structures
Structure: Insulin. Chain: a. Engineered: yes. Other_details: disulfide isomer with disulfide bridges at a6-b7, a7-a11 and a20-b19. Insulin. Chain: b. Engineered: yes. Other_details: disulfide isomer with disulfide bridges at
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli. Expression_system_taxid: 562. Expression_system_taxid: 562
NMR struc: 10 models
Authors: Q.X.Hua,S.N.Gozani,R.E.Chance,J.A.Hoffmann,B.H.Frank, M.A.Weiss
Key ref: Q.X.Hua et al. (1995). Structure of a protein in a kinetic trap. Nat Struct Biol, 2, 129-138. PubMed id: 7749917
10-Oct-96     Release date:   01-Apr-97    
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Protein chain
Pfam   ArchSchema ?
P01308  (INS_HUMAN) -  Insulin
110 a.a.
21 a.a.
Protein chain
Pfam   ArchSchema ?
P01308  (INS_HUMAN) -  Insulin
110 a.a.
30 a.a.
Key:    PfamA domain  Secondary structure

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     extracellular region   1 term 
  Biochemical function     hormone activity     1 term  


Nat Struct Biol 2:129-138 (1995)
PubMed id: 7749917  
Structure of a protein in a kinetic trap.
Q.X.Hua, S.N.Gozani, R.E.Chance, J.A.Hoffmann, B.H.Frank, M.A.Weiss.
We have determined the structure of a metastable disulphide isomer of human insulin. Although not observed for proinsulin folding or insulin-chain recombination, the isomer retains ordered secondary structure and a compact hydrophobic core. Comparison with native insulin reveals a global rearrangement in the orientation of A- and B-chains. One face of the protein's surface is nevertheless in common between native and non-native structures. This face contains receptor-binding determinants, rationalizing the partial biological activity of the isomer. Structures of native and non-native disulphide isomers also define alternative three-dimensional templates. Threading of insulin-like sequences provide an experimental realization of the inverse protein-folding problem.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20724178 M.Liu, I.Hodish, L.Haataja, R.Lara-Lemus, G.Rajpal, J.Wright, and P.Arvan (2010).
Proinsulin misfolding and diabetes: mutant INS gene-induced diabetes of youth.
  Trends Endocrinol Metab, 21, 652-659.  
20336256 Z.Ganim, K.C.Jones, and A.Tokmakoff (2010).
Insulin dimer dissociation and unfolding revealed by amide I two-dimensional infrared spectroscopy.
  Phys Chem Chem Phys, 12, 3579-3588.  
19321435 B.Xu, K.Huang, Y.C.Chu, S.Q.Hu, S.Nakagawa, S.Wang, R.Y.Wang, J.Whittaker, P.G.Katsoyannis, and M.A.Weiss (2009).
Decoding the Cryptic Active Conformation of a Protein by Synthetic Photoscanning: INSULIN INSERTS A DETACHABLE ARM BETWEEN RECEPTOR DOMAINS.
  J Biol Chem, 284, 14597-14608.  
19395706 M.A.Weiss (2009).
Proinsulin and the genetics of diabetes mellitus.
  J Biol Chem, 284, 19159-19163.  
19850922 M.Liu, Z.L.Wan, Y.C.Chu, H.Aladdin, B.Klaproth, M.Choquette, Q.X.Hua, R.B.Mackin, J.S.Rao, P.De Meyts, P.G.Katsoyannis, P.Arvan, and M.A.Weiss (2009).
Crystal structure of a "nonfoldable" insulin: impaired folding efficiency despite native activity.
  J Biol Chem, 284, 35259-35272.
PDB code: 3gky
19321436 Q.X.Hua, B.Xu, K.Huang, S.Q.Hu, S.Nakagawa, W.Jia, S.Wang, J.Whittaker, P.G.Katsoyannis, and M.A.Weiss (2009).
Enhancing the Activity of a Protein by Stereospecific Unfolding: CONFORMATIONAL LIFE CYCLE OF INSULIN AND ITS EVOLUTIONARY ORIGINS.
  J Biol Chem, 284, 14586-14596.
PDB codes: 2k91 2k9r
18515400 G.Lois, J.Blawzdziewicz, and C.S.O'Hern (2008).
Reliable protein folding on complex energy landscapes: the free energy reaction path.
  Biophys J, 95, 2692-2701.  
18260111 W.Bocian, J.Sitkowski, A.Tarnowska, E.Bednarek, R.Kawecki, W.Koźmiński, and L.Kozerski (2008).
Direct insight into insulin aggregation by 2D NMR complemented by PFGSE NMR.
  Proteins, 71, 1057-1065.  
18040865 W.Bocian, J.Sitkowski, E.Bednarek, A.Tarnowska, R.Kawecki, and L.Kozerski (2008).
Structure of human insulin monomer in water/acetonitrile solution.
  J Biomol NMR, 40, 55-64.
PDB code: 2jv1
18491415 W.Bocian, P.Borowicz, J.Mikołajczyk, J.Sitkowski, A.Tarnowska, E.Bednarek, T.Głabski, B.Tejchman-Małecka, M.Bogiel, and L.Kozerski (2008).
NMR structure of biosynthetic engineered human insulin monomer B31(Lys)-B32(Arg) in water/acetonitrile solution. Comparison with the solution structure of native human insulin monomer.
  Biopolymers, 89, 820-830.
PDB code: 2rn5
18004974 Z.Y.Guo, Z.S.Qiao, and Y.M.Feng (2008).
The in vitro oxidative folding of the insulin superfamily.
  Antioxid Redox Signal, 10, 127-140.  
16864583 Q.X.Hua, J.P.Mayer, W.Jia, J.Zhang, and M.A.Weiss (2006).
The folding nucleus of the insulin superfamily: a flexible peptide model foreshadows the native state.
  J Biol Chem, 281, 28131-28142.  
15705595 M.Liu, Y.Li, D.Cavener, and P.Arvan (2005).
Proinsulin disulfide maturation and misfolding in the endoplasmic reticulum.
  J Biol Chem, 280, 13209-13212.  
15096212 C.Y.Min, Z.S.Qiao, and Y.M.Feng (2004).
Unfolding of human proinsulin. Intermediates and possible role of its C-peptide in folding/unfolding.
  Eur J Biochem, 271, 1737-1747.  
15501824 Y.Chen, R.Jin, H.Y.Dong, and Y.M.Feng (2004).
In vitro refolding/unfolding pathways of amphioxus insulin-like peptide: implications for folding behavior of insulin family proteins.
  J Biol Chem, 279, 55224-55233.  
12446709 B.Y.Zhang, M.Liu, and P.Arvan (2003).
Behavior in the eukaryotic secretory pathway of insulin-containing fusion proteins and single-chain insulins bearing various B-chain mutations.
  J Biol Chem, 278, 3687-3693.  
14500892 C.B.Millard, V.L.Shnyrov, S.Newstead, I.Shin, E.Roth, I.Silman, and L.Weiner (2003).
Stabilization of a metastable state of Torpedo californica acetylcholinesterase by chemical chaperones.
  Protein Sci, 12, 2337-2347.  
12724517 M.Cemazar, S.Zahariev, J.J.Lopez, O.Carugo, J.A.Jones, P.J.Hore, and S.Pongor (2003).
Oxidative folding intermediates with nonnative disulfide bridges between adjacent cysteine residues.
  Proc Natl Acad Sci U S A, 100, 5754-5759.  
12590147 M.Liu, J.Ramos-Castañeda, and P.Arvan (2003).
Role of the connecting peptide in insulin biosynthesis.
  J Biol Chem, 278, 14798-14805.  
12631285 T.Yamazaki, M.Takaoka, E.Katoh, K.Hanada, M.Sakita, K.Sakata, Y.Nishiuchi, and H.Hirano (2003).
A possible physiological function and the tertiary structure of a 4-kDa peptide in legumes.
  Eur J Biochem, 270, 1269-1276.
PDB code: 1ju8
12624089 Z.S.Qiao, C.Y.Min, Q.X.Hua, M.A.Weiss, and Y.M.Feng (2003).
In vitro refolding of human proinsulin. Kinetic intermediates, putative disulfide-forming pathway folding initiation site, and potential role of C-peptide in folding process.
  J Biol Chem, 278, 17800-17809.  
12196530 Q.X.Hua, Y.C.Chu, W.Jia, N.F.Phillips, R.Y.Wang, P.G.Katsoyannis, and M.A.Weiss (2002).
Mechanism of insulin chain combination. Asymmetric roles of A-chain alpha-helices in disulfide pairing.
  J Biol Chem, 277, 43443-43453.
PDB code: 1lkq
11814349 Z.Y.Guo, L.Shen, and Y.M.Feng (2002).
The different folding behavior of insulin and insulin-like growth factor 1 is mainly controlled by their B-chain/domain.
  Biochemistry, 41, 1556-1567.  
12186542 Z.Y.Guo, L.Shen, and Y.M.Feng (2002).
The different energetic state of the intra A-chain/domain disulfide of insulin and insulin-like growth factor 1 is mainly controlled by their B-chain/domain.
  Biochemistry, 41, 10585-10592.  
11517220 M.A.Weiss, Q.X.Hua, W.Jia, S.H.Nakagawa, Y.C.Chu, S.Q.Hu, and P.G.Katsoyannis (2001).
Activities of monomeric insulin analogs at position A8 are uncorrelated with their thermodynamic stabilities.
  J Biol Chem, 276, 40018-40024.  
11296285 N.E.Robinson, and A.B.Robinson (2001).
Prediction of protein deamidation rates from primary and three-dimensional structure.
  Proc Natl Acad Sci U S A, 98, 4367-4372.  
18763100 Y.Huang, Z.Liang, and Y.Feng (2001).
The relationship between the connecting peptide of recombined single chain insulin and its biological function.
  Sci China C Life Sci, 44, 593-600.  
11258877 Z.S.Qiao, Z.Y.Guo, and Y.M.Feng (2001).
Putative disulfide-forming pathway of porcine insulin precursor during its refolding in vitro.
  Biochemistry, 40, 2662-2668.  
11083061 A.Sato, S.Koyama, H.Yamada, S.Suzuki, K.Tamura, M.Kobayashi, M.Niwa, T.Yasuda, Y.Kyogoku, and Y.Kobayashi (2000).
Three-dimensional solution structure of a disulfide bond isomer of the human insulin-like growth factor-I.
  J Pept Res, 56, 218-230.  
11112528 M.A.Weiss, Q.X.Hua, W.Jia, Y.C.Chu, R.Y.Wang, and P.G.Katsoyannis (2000).
Hierarchical protein "un-design": insulin's intrachain disulfide bridge tethers a recognition alpha-helix.
  Biochemistry, 39, 15429-15440.  
9501918 A.R.Dinner, and M.Karplus (1998).
A metastable state in folding simulations of a protein model.
  Nat Struct Biol, 5, 236-241.  
9538685 R.J.Ellis (1998).
Steric chaperones.
  Trends Biochem Sci, 23, 43-45.  
9578575 V.Prasanna, S.Bhattacharjya, and P.Balaram (1998).
Synthetic interface peptides as inactivators of multimeric enzymes: inhibitory and conformational properties of three fragments from Lactobacillus casei thymidylate synthase.
  Biochemistry, 37, 6883-6893.  
9566117 C.McInnes, and B.D.Sykes (1997).
Growth factor receptors: structure, mechanism, and drug discovery.
  Biopolymers, 43, 339-366.  
  9232650 F.Tani, N.Shirai, T.Onishi, F.Venelle, K.Yasumoto, and E.Doi (1997).
Temperature control for kinetic refolding of heat-denatured ovalbumin.
  Protein Sci, 6, 1491-1502.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.